The Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) is a biomedical research center funded through a pioneering public-private partnership between the Spanish Government and the Pro CNIC Foundation (composed of eleven Spanish companies unrelated to the biomedical sector). The CNIC is a Severo Ochoa Center of Excellence of Spain's Ministry of Science and Innovation. The Center also benefits from the external support of its Scientific Advisory Board, composed of leading international experts who provide guidance on strategy and regularly assess the performance of the Center and its program projects and group leaders.
Cardiovascular disease (CVD) is the principal cause of death worldwide, and the exponential increase in the cost of treating CVD in its symptomatic phase places an insurmountable burden on patients, families, and health systems. In response to this challenge, the CNIC has defined three major goals: to increase the understanding of cardiovascular health, to improve disease prevention, and to generate treatment advances for the prevalent manifestations of CVD. These goals require mechanistic studies to gain insight into the molecular and cellular processes underlying disease, clinical studies and the translation of these findings into improvements in health promotion, diagnosis, and disease management.
To meet these challenges, the CNIC has four pillars: excellence in basic and clinical research, technology, networking and training.
CNIC scientific area is organized into two departments focused on Basic Research and Clinical Research, fully interconnected through seven highly focused and integrated programs: (1) novel mechanisms of atherosclerosis, (2) myocardial homeostasis & cardiac injury, (3) cardiovascular regeneration, (4) novel arrhythmogenic mechanisms, (5) CVD, risk factors & brain health, (6) cardiovascular health promotion, and (7) technology development. These programs span from basic research to advanced health-changing clinical trials and build on the CNIC’s deep-rooted and proven expertise in state-of-the-art technology, cellular and other experimental models, imaging modalities, and large-scale data gathering and analysis.
In 2023, CNIC recruited three Group Leaders, Dr Inés García Lunar in the novel mechanisms of atherosclerosis program, Dr Ana García Álvarez in the myocardial homeostasis and cardiac injury program and Dr Florian Weinberger in the cardiovascular regeneration program.
According to the SCImago Institutions Ranking, the CNIC was evaluated in 2023 as the second-best cardiovascular research centre in the world, just behind the National Heart Lung and Blood Institute, which depends on the US NIH, and the CNIC is even ahead in the area of innovation.
The Center’s eleven translational studies, including several large randomized clinical trials, have already changed clinical practice worldwide. These studies bear testimony to the enthusiastic commitment of researchers, healthy volunteers, patients, and emergency service personnel to defining the causes and risk factors of CVD. The most recent clinical practice guidelines of the European Society of Cardiology for the year 2023, focusing on both the Treatment of Cardiomyopathies and the Treatment of Acute Coronary Syndromes, have integrated 13 references from specialized work of the CNIC. The importance of these guidelines is based on the fact that the recommendations they offer for clinical practice come from the best existing scientific evidence.
The CNIC's most important patent is the polypill. A major milestone in 2023 was the inclusion of the polypill developed by the CNIC and Ferrer Laboratories in the World Health Organisation's (WHO) List of Essential Medicines. Marketed in 29 countries, this drug, which allows patients to take a single daily pill after a heart attack, is not only a more convenient option, it also saves lives. The polypill has been shown to be effective in preventing cardiovascular events after a heart attack by reducing cardiovascular events by 24% and cardiovascular death by 33% in patients who have previously suffered a myocardial infarction. Other important 2023 findings in basic, translational and clinical research are included in the section of Scientific Highlights.
As we move forward, the CNIC will maintain the drive and focus established in its initial phases and ensure that the Center’s basic and clinical scientists continue to work closely together to devise innovative projects that help reduce the health and socioeconomic burden associated with CVD and to train the researchers of the future.
The CNIC is organized into two departments, one focused on Basic Research and the other on Clinical Research. Research in these fields is fully interconnected through seven focused Programs.
The Novel Mechanisms of Atherosclerosis Program aims to provide key insights into the pathophysiology of atherosclerosis, the underlying cause of the most frequent cardiovascular and cerebrovascular disorders. Despite the efficacy of interventions that target traditional cardiovascular risk factors, a substantial risk of atherosclerotic cardiovascular disease remains, even in individuals who achieve massive reductions in blood cholesterol and are apparently at low cardiovascular risk based on current risk scores. Therefore, while it remains imperative to target well-established cardiovascular risk factors, there is an evident need for a deep understanding of non-conventional risk factors and pathophysiological mechanisms that could lead to new strategies for the prediction, prevention, and treatment of atherosclerotic cardiovascular disease. In this context, the research groups in the Program are working towards the identification and characterization of new inflammatory drivers of atherosclerosis.
Research during the past 30 years has clearly established that atherosclerosis is an inflammatory condition resulting from a maladaptive response of the immune system to the chronic exposure to cardiovascular risk factors. Despite this, targeting inflammation in cardiovascular disease remains an unfulfilled promise, highlighting the need for a comprehensive understanding of the intricacies of inflammatory responses in atherosclerosis. Several research groups in the Program are working towards this goal, building upon prior seminal work and combining human studies (based on existing and novel data from the Progression of Early Subclinical Atherosclerosis [PESA] cohort) and experiments in different models. Ongoing research in this area is focused on the role of acquired mutations in hematopoietic cells (a phenomenon called clonal hematopoiesis), telomere dynamics, autoantibodies, and specific leukocyte subsets in atherosclerosis. Additional projects are related to the biology of vascular smooth muscle cells in atherosclerotic plaques, the sensing of mechanical stress by the vascular wall, the effects of microbiota-derived metabolites, and the identification of circulating and imaging biomarkers of atherosclerosis development.
In 2023, among other research achievements, scientists in the Program identified key determinants of human atherosclerosis dynamics during its early, asymptomatic stages. Program scientists also expanded our knowledge of the regulation and function of immune cells at multiple levels. We demonstrated that acquired p53 gene mutations accelerate atherosclerosis development by exacerbating macrophage proliferation within atherosclerotic plaques. We also established that macrophage function is tightly regulated by mitochondrial respiration, which is highly dependent on the organ microenvironment. Furthermore, research into the sensing of mechanical stress by the vascular wall have identified novel plasma membrane invaginations called dolines that respond to weak or medium-strength mechanical forces.
The quality and potential of the research conducted by the Program teams is attested by several successful applications for research funding in 2023, including research grants funded by La Caixa Foundation, La Marató de TV3 Foundation, the ERA4Health CARDINNOV program, the ERC Proof of Concept program, and the EIC Pathfinder program. This new funding will fuel further developments in our scientific project. In addition, among other awards received by Program scientists, Dr David Sancho was garlanded with the 28th Carmen and Severo Ochoa Award for Research in Molecular Biology.
The Program place great emphasis on the effective public communication of our research into atherosclerotic cardiovascular disease. Last year, Program scientists participated in several outreach activities, most notably the Cardioguía: más allá del colesterol alto event, held as part of the XXIII Science and Innovation Week in Madrid.
Molecular and Genetic Cardiovascular Pathophysiology
Experimental Pathology of Atherosclerosis
Mechanoadaptation and Caveolae Biology
Hematovascular Pathophysiology
Cardiovascular Imaging and Population Studies
Cardiovascular Prevention through Non-invasive Imaging
Nanomedicine and Molecular Imaging
B Lymphocyte Biology
Intercellular Communication in the Inflammatory Response
Immunobiology
Cardiovascular Proteomics
The research groups in the Myocardial Homeostasis and Cardiac Injury (MERCURY) Program investigate the genetic, molecular, and biomechanical mechanisms underlying myocardial injury and the development of inherited cardiomyopathies. MERCURY groups also investigate the development of new therapies based on these mechanisms.
Despite the development of diverse cancer therapies, for many cancers the first line treatment remains chemotherapy with anthracyclines. One of the most feared adverse effects of these drugs is irreversible cardiac injury, which affects many patients. Alternative treatments include immune checkpoint inhibitors (ICIs), which are monoclonal antibodies that target host negative immune regulatory receptors. While effective for cancer treatment, this approach can also be cardiotoxic, inducing myocarditis, which is associated with high mortality. Understanding remains limited about the mechanisms through which anthracyclines and ICIs induce cardiac damage, as well as the factors that determine variable interindividual vulnerability to these cytotoxic effects. This knowledge deficit translates into a lack of effective therapies able to prevent or reverse this cardiac pathology.
A major goal of the MERCURY Program is therefore to define the pathways and mechanisms underlying the cardiotoxic effects triggered by anthracyclines and ICIs used to treat cancer. We aim to identify the main determinants of this type of myocardial injury and then to develop new therapeutic approaches based on the inhibition of these pathways.
A second main area of interest of the MERCURY Program investigators is the genetic basis of inherited cardiomyopathies (CMs). Genetic testing has evolved rapidly over the last decade and is now an established element of the clinical management of CM patients and their families. Despite this, the current yield of genetic testing, even in familial cases (with two or more family members affected), is around 40%, and most cases remain unexplained. Furthermore, most genetic heart conditions are treated with drugs developed for generic cardiac pathologies, such as heart failure or cardiac arrhythmias. For most CMs, there are no specific disease-modifying treatments.
Our researchers are working to identify new disease-causing mutations in noncoding regions, chiefly introns, and are investigating the molecular basis of genetic cardiomyopathies. We are also developing large animal models of hypertrophic and arrhythmogenic cardiomyopathies, based on the success of our previous mouse models, and we aim to use these models to develop new gene therapy tools and identify small molecules with the potential to improve cardiac function.
The MERCURY Program relies on the combination of our research teams’ strong complementary expertise in biomechanics, molecular biology, physiology, immunology, and genetics. This complementary approach provides each task with additional granularity. The program has a clear translational orientation, aimed at developing new diagnostic and therapeutic tools.
Molecular Mechanics of the Cardiovascular System
Heart Failure and Pulmonary Hypertension Translational Research
Inherited Cardiomyopathies
Translational Laboratory for Cardiovascular Imaging and Therapy
Molecular Regulation of Heart Failure
The Cardiovascular Regeneration (CVR) Program aims to understand basic principles of heart and vasculature development and regeneration and to use this knowledge to develop new therapeutic strategies to cure cardiovascular diseases. Within this field, the CVR Program has a strong focus on the metabolic regulation of cardiac regenerative ability.
In the metabolic regulation area, a CVR collaborating group led by Dr Mercedes Ricote demonstrated that the gamma-linolenic acid–retinoid X receptor axis is a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism. The study showed that RXRs in cardiomyocytes relay signals form maternal milk-derived fatty acids to enable mitochondrial maturation and metabolic adaptation in neonatal hearts.
These results reinforce the idea that mother–infant interactions in early life are major drivers of organismal physiology and cardiac health and address a crucial period of heart development during which the natural regenerative ability of the fetal heart is lost. Along these lines, the CVR group led by Dr Jose Antonio Enríquez continued efforts to understand and control the regulation of mitochondrial oxidative phosphorylation (OxPhos). Their work demonstrated the role of cox7a1 in striated muscle maturation through regulation of the respiratory chain, uncovering a direct connection between mitochondrial flavin homeostasis and complex I stability and assembly. This finding paves the way for novel pharmacological strategies to regulate respiratory complex I. In a further collaborative study, Drs Enríquez and Muñoz-Cánoves showed that the loss of mitochondrial fission in skeletal muscle satellite cells—due to aging or genetic impairment—dysregulates the mitochondrial electron transport chain, leading to inefficient OxPhos metabolism, mitophagy, and increased oxidative stress. These findings have implications for regeneration therapies in sarcopenia. Also in this area, Drs Nadia Mercader and Enríquez used the zebrafish model to examine the effects of cox7a1 and cox7a2l loss-of-function on the physiology and injury response of skeletal muscle and myocardium, revealing a high Cox7a-isoform specificity in the control of supercomplex assembly and striated muscle metabolism.
Mechanistic studies of heart diseases with a developmental basis included a study led by Dr Rui Benedito which showed that single-cell transcriptional states, or the dysregulation of transcriptional factor networks, often do not correlate with vascular pathophysiological cell states, a finding that challenges the sole use of scRNAseq transcriptome analysis to predict vascular phenotypes, states, or diseases.
In another study, the group led by José Luis de la Pompa uncovered a new mechanistic basis for congenital heart disease, establishing the causal relationship between disrupted NOTCH-MIB1 signaling and human congenital heart defects (left ventricular noncompaction and bicuspid aortic valve). In a second study, these scientists identified a mechanistic link between NOTCH, NRG1, and HIPPO signaling in the regulation of cardiomyocyte proliferation and cellular dynamics during early cardiac chamber development.
2023 was a transitional year for the CVR Program, with several groups leaving and others joining. Dr Andrés Hidalgo has been transitioning to his new location at Yale University but has continued to participate in the CVR Program. His group has continued its studies of the roles of neutrophils and macrophages in vascular health and cardiac homeostasis, discovering that the contribution of macrophages to cardiomyocyte proteostasis extends to other organs and is adaptable to the metabolic status of the organ. The groups of Pura Muñoz-Cánoves and Mercedes Ricote also left the CNIC last year, but both maintain collaborative bonds with the CVR Program. Dr Florian Weinberger joined the Program as a new group leader in September 2023. He leads the Cardiac tissue engineering and regenerative therapies group, which aims to develop stem-cell based strategies to remuscularize the failing heart. Their research combines cardiac tissue engineering with chemo- and optogenetic tools to dissect mechanisms of cardiac regeneration. Dr Weinberger´s incorporation contributes essential expertise in IPSC-derived cardiomyocytes, supporting CVR Program plans to set up drug screening, in vitro disease modeling, and regenerative strategies. Recent recruit Dr Hesham Sadek consolidated his group at the CNIC during 2023 and is developing projects aimed at discovering new drugs for heart regeneration based on the transcriptional control of cardiomyocyte proliferation.
In the area of technology development, Dr Nadia Mercader established a screening pipeline that uses zebrafish larvae to assess the effect on cardiovascular development of compounds used to treat COVID-19. The pipeline can be expanded to perform further drug screens within the CVR Program. In addition, the Program is developing centralized technology platforms and has hired a technician for animal models and non-invasive imaging and a senior postdoc to set up an IPSC-derived cardiomyocyte high-throughput screening platform.
Molecular Genetics of Angiogenesis
Intercellular Signaling in Cardiovascular Development and Disease
Functional Genetics of the Oxidative Phosphorilation System (GENOPHOS)
Imaging the Cardiovascular Inflammation and the Immune Response
Cardiac Arrhythmia
Development of the epicardium and its role during regeneration
Tissue Regeneration
Nuclear Receptor Signaling
Myocardial regeneration via cardiomyocyte cell cycle regulation
Genetic Control of Organ Development and Regeneration
Cardiac Tissue Engineering and Regenerative Therapies
Cardiac arrhythmias may be partially linked to underlying non-arrhythmogenic phenotypes. We have used mouse models of catecholaminergic polymorphic ventricular tachycardia (CPVT1) and the recessively inherited triadin knockout (KO) syndrome to detect the presence of uncharacterized non-arrhythmogenic phenotypes that might contribute to the arrhythmias observed in these diseases. In both models, we detected dysfunctional phenotypes in mitochondria. Characterization of the mitochondrial phenotype in cardiomyocytes from the CPVT1 model revealed that CPVT1 mitochondria are calcium-overloaded, have disrupted structure and ATP synthesis, and generate elevated amounts of mitochondrial reactive oxygen species (mitoROS). These mitoROS have the potential to diffuse out from mitochondria, increasing the probability of arrhythmias. A similar analysis is underway to characterize disturbed mitochondrial function in Triadin-KO hearts.
We have also observed a pronounced destabilization of the tubulin cytoskeleton in cells from triadin-KO hearts (Figure 1). This microtubular destabilization leads to mistargeting and degradation of calsequestrin 2, a protein that stabilizes the sarcoplasmic reticulum calcium release complex. Thus, in triadin-KO hearts, a cytoskeletal phenotype could be partially responsible for the observed changes in calcium handling that trigger arrhythmias.
These experiments are the subject of two Ph.D. theses. The project investigating CPVT1 has already been defended, while the one investigating triadin-KO syndrome is in progress.
We have created the first knock-in swine model of Timothy Syndrome type 1, a devastating inherited arrhythmogenic disease associated with a median life expectancy <5 years. Extensive characterization of the arrhythmogenic substrate in single cells and whole hearts identified 3 previously uncharacterized mechanisms in the context of this disease that contribute to arrhythmia. The first is an unexpected calcium–overload-dependent and CaMKII-dependent slowing of conduction that promotes re-entrant arrhythmias. The other 2 mechanisms are an increased sodium late current and the fusion of late-systolic calcium sparks (leading to enhanced Na–Ca exchange). Together with the increased calcium current characteristic of Timothy Syndrome, these newly identified mechanisms contribute to dispersion of repolarization throughout the heart.
We have further tested 5 pharmacological therapies aimed at 3 separate points along the intricate pathway leading to arrhythmias in Timothy Syndrome, while simultaneously demonstrating the suitability of a whole-heart metric for improved diagnosis of arrhythmogenic risk (difficult to assess in patients) (Figure 2). These findings were recently published in Nature Cardiovascular Research alongside an accompanying editorial.
To model Timothy Syndrome in a human context, we have developed a human iPSC-derived cardiomyocyte cell line that replicates the phenotype.
Ventricular remodeling after myocardial infarction generates a potential proarrhythmic substrate. However, the interplay between the structural and functional substrates for ventricular tachycardia (VT) maintenance is not completely understood. During the last few years, we have studied the scar and fiber disorganization substrate associated with functional alterations during ventricular pacing and VT mapping. Fourteen pigs with an infarct-related substrate were investigated by state-of-the-art cardiac imaging and invasive mapping procedures to identify the functional and structural properties associated with abnormal wave-front propagation and VT maintenance. The results show that deceleration zones during ventricular pacing and critical isthmus sites during VT mapping share similar underlying scar properties and myocardial fiber disorganization.
However, deceleration zones derived from one pacing location were not sufficient to identify critical VT isthmus sites in all animals. These data indicate that proper identification of the substrate associated with VT isthmus sites during pacing may require pacing maneuvers from more than one location. This work was presented in the Rosanna Degani Young Investigator Finals at the 2023 Computing in Cardiology Meeting in Atlanta.
https://cinc.org/final_program_papers_2023
Advanced Development in Arrhythmia Mechanisms and Therapy
Molecular Cardiology
This program studies the mechanisms involved in the cognitive impairment associated with cardiovascular disease and its risk factors, such as hypertension, high cholesterol, obesity, and metabolic syndrome. Our aim is to use the knowledge gained to promote cardiovascular health and to develop strategies to prevent the appearance of cognitive impairment with age.
Cardiovascular disease and dementia often coincide in advanced stages, and controlling cardiovascular risk factors in midlife may lower dementia risk later on. However, little attention has been paid in the past to how atherosclerosis and its risk factors affect brain health in midlife. In a first cross-sectional study of participants with subclinical atherosclerosis from the PESA study, researchers from the Cardiovascular Risk Factors and Brain Health Program (CRFBP) found that subclinical atherosclerosis and vascular risk were associated with cerebral hypometabolism in asymptomatic individuals aged 50 years (Cortés-Canteli et al. JACC 2021). In 2023, a longitudinal study of a subgroup of PESA participants with subclinical atherosclerosis (n=370) showed that those with persistently high cardiovascular risk experienced a faster decline in brain glucose consumption, partly as a consequence of neurodegeneration. Progression of subclinical carotid atherosclerosis was also linked to further declines in brain metabolism, particularly in areas vulnerable to Alzheimer’s disease. These findings highlight the importance of maintaining cardiovascular health in midlife as a way to potentially reduce neurodegenerative diseases later on (Tristao-Pereira et al. Lancet Healthy Longev. 2023 Sep;4(9):e487-e498; Fig. 1).
Stroke is a model condition for studying the impact of cardiovascular risk factors on the cerebral vascular system and its neurobiological targets. Previous research by program members showed an association between post-stroke cognitive impairment and aberrant hippocampal neurogenesis (Cuartero et al. JCI 2019). Building on this finding, CRFBP scientists recently used noninvasive magnetic resonance spectroscopy to show that this cognitive impairment is mediated by an ipsilesional metabolic imbalance, thus providing novel diagnostic and therapeutic targets for the prevention of post-stroke cognitive impairment (Torres et al. Stroke. 2023 Oct;54(10):2652-2665; Figs 2 & 3).
Program members also contributed to the development of a new drug with demonstrated efficacy in reducing mortality and disability in stroke patients (Hernández-Jiménez et al. JAMA Neurol. 2023 Aug 1;80(8):779-788; Fig. 4).
Another area of interest is how brain function is impacted by obesity and how this interaction is influenced by exercise. A study currently under editorial review characterizes the signaling pathway modulated by the myokine Il15, which plays a crucial role in this communication network, particularly affecting the motor cortex. (Herrera-Melle et al., Remodeling p38 Signaling in Muscle Controls Locomotor Activity via IL-15. Sci Adv under 2nd editorial review).
Several program members participated last year in the production of a series of articles for a themed issue of Br. J. Pharmacol. published in January 2024) called From Alzheimer's disease to vascular dementia: Different roads leading to cognitive decline (Fig. 5).
Multidisciplinary Translational Cardiovascular Research (MTCR)
Cardiovascular Imaging and Population Studies
Regulatory Molecules of Inflammatory Processes
Neurovascular Pathophysiology
Gene regulation in Cardiovascular Remodelling and Inflammation
Stress kinases in Diabetes, Cancer and Cardiovascular Disease
Cardiovascular disease (CVD) is one of the leading causes of death and disability worldwide, and its high prevalence and impact are largely the result of risk factors that can be modified by changes in behavior (smoking, an unhealthy diet, physical inactivity, etc.). The problem is expected to get worse in the coming years due to the disturbing increase in the prevalence of unhealthy lifestyles and obesity, particularly among children.
The research teams in the Cardiovascular Health Promotion Program (CHPP) work on multidisciplinary studies and clinical trials in close collaboration with schools and communities. These studies target both children and adults and are aimed at implementing early prevention strategies and developing research applications for noninvasive technologies to support translational research and population studies on preclinical atherosclerosis.
The ultimate goal of the CHPP is to implement health promotion and prevention strategies as an effective means of reducing the personal and societal burden of CVD and potentially increasing life expectancy free of other diseases such as dementia and cancer. The key objectives of the Program are as follows:
The Program comprises 2 research groups: the Cardiovascular Imaging and Population Studies group (PI, Valentin Fuster) and the Cardiovascular Health and Imaging Lab (PI, Rodrigo Fernández-Jiménez). Projects and activities developed during 2023 generated relevant scientific advances, some of which are highlighted below.
Through an analysis of data from the PESA study, CNIC researchers from the CHPP demonstrated that insulin resistance (measured as the homeostatic model assessment of insulin resistance index; HOMA-IR) identifies individuals with a low CVD risk who have an elevated burden of subclinical atherosclerosis, independently of the effects of key traditional cardiovascular risk factors and glycated hemoglobin. These findings suggest that HOMA-IR can be used as a simple measure to facilitate earlier implementation of primary cardiovascular prevention strategies in clinical practice [Cardiovasc Diabetol. 2023;22(1):350.doi: 10.1186/s12933-023-02090-1. Figure 1]
CHPP scientists also reported the primary results of the SI! Program for Secondary Schools trial, a 4-year cluster randomized intervention trial conducted in 24 secondary schools in Barcelona and Madrid. This trial assesses the effect of 2 multicomponent educational health promotion strategies of differing duration and intensity on cardiovascular health in adolescents. Although there was evidence of some beneficial effects at a point midway through the long version of the intervention, further implementation was affected by the COVID-19 pandemic and no benefit was noted at the end of the trial [JAMA Cardiol. 2023;8(9):816-824.doi: 10.1001/jamacardio.2023.2231].
In another study of data from the SI! Program for Secondary Schools trial, accelerometry-measured sleep duration was analyzed for cross-sectional and longitudinal associations with adiposity markers in adolescence. Strikingly, most adolescents did not meet sleep recommendations, and shorter sleep duration was independently and cumulatively associated with unfavorable adiposity markers [Eur J Prev Cardiol. 2023;30(12):1236-1244.doi: 10.1093/eurjpc/zwad137. Figure 2]. These results emphasize the importance of including good sleep habits as a key element of health promotion programs.
The CHPP recognizes the crucial importance of effective communication to increase public visibility and awareness of cardiovascular health and healthy lifestyle habits. Program scientists participated in several outreach activities during 2023, most notably “Cardioguía: más allá del colesterol alto” event, held as part of the XXIII Science and Innovation Week in Madrid.
Cardiovascular Health and Imaging
Cardiovascular Imaging and Population Studies
The 11 Technical Units (TUs) that make up the Technology Development Program (TDP) work to keep the CNIC at the forefront of cardiovascular research by developing and implementing cutting-edge biomedical technologies, providing internal and external services, and engaging in training and scientific collaborations in funded projects https://www.cnic.es/en/investigacion/unidades-tecnicas
Our work falls into 4 key areas:
Training is one of the CNIC’s core activities and enjoys the TDP’s commitment and support through the participation of the TUs in the UAM Master’s in Molecular Biomedicine (BMM7) and other scientific training and communication programs, such as Acércate, Res@cnic, and the seminar program. The TUs also participate in high-impact external activities such as the organization of the XVIII Congress of the Iberian Society of Cytometry; Cost Action (CA) 20140 (CorEuStem, The European Network for Stem Cell Core Facilities); CA21113 (GeneHumDi, Genome Editing for the Treatment of Human Disease Network); and CA21151 (HaploiPSCs, Generation of human induced pluripotent stem cells from haplo-selected cord blood samples).
In 2023, the CNIC TUs published 82 articles, accounting for 28% of the total CNIC scientific production. Also last year, all the TUs for the first time applied jointly as the Technology Development Program to the ISCIII call for platforms.
Through its efforts to unify the organization of the TUs, the TDP has been able to make significant progress towards ISO certification, which is expected to be completed for all the TUs in 2024.
Bioinformatics
Clinical Trial Coordination
Flow Cytometry
Genomics
Imaging
Microscopy
Pluripotent Cell Technology
Proteomics
Transgenesis
Viral Vectors
(PESA-Health-CNIC-Santander Study)
Principal investigator: Valentín Fuster
The PESA-Health-CNIC-Santander study is the natural continuation of the long-term endeavor begun in 2010 with the PESA Study, directed by the CNIC in collaboration with Santander Bank. In PESA-Health, the PESA participants enrolled in 2010 (4184 asymptomatic individuals between the ages of 40 and 55 years at enrollment) are being followed up over an additional 10 years.
The PESA study sought to identify the presence of subclinical atherosclerosis (SA) long before symptoms appear and to understand the cues leading to its development and progression. PESA-Health expands these goals to new areas, including the correlation of SA with Alzheimer’s and cognitive diseases, the acquisition of somatic mutations with aging, and the correlation of these mutations with increasing cardiovascular event rates and SA progression. PESA-Health continues to make good use of the opportunities offered by state-of-the-art imaging technologies, including 3D vascular ultrasound of the carotid arteries and aorta, coronary artery calcium quantification by computed tomography, cardiac magnetic resonance, AngioTC, PET, and PET-amyloid analysis. And, just as in the PESA study, PESA-Health includes biosampling for extensive omics analysis. New state-of-the-art substudies in PESA-Health include investigation of the relationship between sleep apnea and SA.
PESA-Health is the CNIC’s flagship study, and several CNIC clinical and basic research groups participate in it. The PESA study findings are already making seminal contributions to our understanding of the origin and progression of atherosclerosis.
The PESA-Health-CNIC-Santander study welcomed its first participant in February 2020. By the end of 2023, 3484 participants had agreed to continue their participation, with around 3000 of them having completed their first PESA-Health visit.
(RESILIENCE)
Principal investigator: Borja Ibáñez
H2020 Grant# 945118
Anthracyclines are a class of anticancer drugs that are widely used to treat many cancers. Of the 4 million new cancer cases diagnosed in Europe every year, >3 million receive anthracyclines (alone or in combination with other treatments). Very recent data show that >35% of patients receiving anthracyclines develop some form of cardiomyopathy. The trade-off between cancer and chronic heart failure (HF) places an immense psychological burden on cancer survivors, and for healthcare systems the growing incidence of chronic HF is a devastating consequence of cancer treatment.
Remote ischemic pre-conditioning (RIPC) is a process in which brief, reversible episodes of ischemia followed by reperfusion in one region (e.g. an arm) render remote tissues and organs resistant to injury. RIPC is safe and effective, noninvasive, feasible, and inexpensive. There is abundant experimental evidence that large animals undergoing 3 to 5 cycles of brief (5 min) limb ischemia followed by 5 min reperfusion have a degree of protection against subsequent induced myocardial infarction, having smaller infarcts than animals undergoing myocardial infarction without preceding cycles of RIPC. Recent evidence suggests that, to be protective, RIPC needs to be initiated before the index insult. Anthracycline-induced cardiomyopathy provides an ideal setting for testing this hypothesis because chemotherapy is a planned procedure.
RESILIENCE is a multinational prospective proof-of-concept phase II, double-blind, sham-controlled, randomized controlled trial evaluating the efficacy and safety of RIPC in patients with non-Hodgkin lymphoma (NHL) and receiving anthracyclines. Patients scheduled to undergo ≥3 chemotherapy cycles and fulfilling all inclusion and no exclusion criteria will be enrolled and undergo baseline cardiac magnetic resonance (CMR) imaging and a high sensitivity troponin (hsTn) and NT-proBNP blood test. Patients with confirmed LVEF >40% by CMR will be randomized 1:1 to RIPC or simulated RIPC (Sham).
Nine weeks after finishing chemotherapy, patients will undergo a final CMR+ hsTn/NT- proBNP test. All patients will be followed up for clinical events at 12, 18, 30, and 42 months until the last patient undergoes the final CMR.
The RESILIENCE Trial aims to recruit 608 patients in 6 European countries (Spain, Portugal, France, Germany, the Netherlands, and Denmark) and is funded by the European Commission (Grant Agreement-945118-RESILIENCE). The grant period began in June 2021, and in 2022 patient recruitment began at 11 sites. By the end of 2023 all 18 sites were opened, with 157 participants enrolled.
(REBOOT)
Principal investigator: Borja Ibáñez
The prescription of beta-blockers to patients after a myocardial infarction (MI) is based on evidence from trials performed in the pre-reperfusion era. While there is solid evidence for the benefit of these drugs in post-MI patients with reduced ejection fraction, evidence is lacking for patients with a preserved ejection fraction. Despite this, more than 80% of post-MI patients in this category are prescribed beta-blockers for the rest of their lives. REBOOT is a multinational trial that will enroll 8600 post-MI patients with a left ventricular ejection fraction >40%. Patients are randomized to beta-blocker therapy (type and dose decided by the attending physician) or to no treatment. The primary endpoint is the composite of all-cause death, reinfarction, or heart failure admission during 3-year follow-up. This trial is coordinated by the CNIC Clinical Trials Coordination Unit and is run in close collaboration with the Mario Negri Institute of Pharmacological Research in Milan. In total, 77 hospitals in Spain and 29 in Italy are participating in this large-scale project, which will have a major impact on clinical practice.
The first patients were enrolled in October 2018, and 8400 had been recruited by the end of January 2024. Enrollment will be completed during the first quarter of 2024.
(MRVALVE)
Principal investigator: Borja Ibáñez
The consequences of valvular heart disease (VHD) on left ventricular (LV) dimensions, function, and tissue composition are important determinants in clinical decision-making. Current practice guidelines recommend surgical treatment for patients with significant VHD when symptoms develop or when there is LV remodeling or dysfunction. The most prevalent valvulopathies are aortic valve stenosis (AS) and mitral regurgitation (MR). Transition from asymptomatic to symptomatic disease or from normal LV dimensions and function to LV dilatation/hypertrophy (LVH) and dysfunction is determined by changes in tissue composition (predominantly cardiomyocyte death, extracellular volume expansion, and fibrosis). The current therapies for severe VHD are surgery or percutaneous valve repair or replacement, and the decision to intervene is based on the presence of symptoms and/or gross anatomical and functional LV involvement, evident as significant chamber dilatation or reduced ejection fraction. When these features appear, it is often too late for interventions to fully restore heart function. There is therefore a need for tools for the early detection of myocardial involvement in patients with asymptomatic VHD, to enable appropriate intervention before overt deterioration of heart function. Cardiac magnetic resonance (CMR) is the gold standard for anatomical and functional cardiac assessment, including the detection of focal areas of fibrosis by late gadolinium enhancement (LGE) after contrast-gadolinium administration. Moreover, highly accurate tissue characterization is available with recent CMR advances such as parametric T1/T2 mapping, absolute myocardial perfusion quantification, extracellular volume calculation (a surrogate of diffuse fibrosis), and tagging. The assessment of focal and diffuse fibrosis requires endovenous contrast. We will use the contrast agent gadolinium, which has a superior safety profile and is in routine clinical use. Assessment of diffuse fibrosis also requires a blood sample for determination of the hematocrit. For the study of active deformation of the LV myocardium, the best imaging modality is strain echocardiography, which can detect impaired multidirectional strain (active deformation) even when overall LV function is preserved. We will correlate the imaging data with functional data from the 6-minute walking test, which provides an objective assessment of functional exercise capacity. The amount and extent of calcium deposition in the coronary arteries and heart valves will be assessed by cardiac computed tomography, a noninvasive method that gives the calcium score, which is a diagnostic and prognostic tool in AS patients. This project will use a multimodality imaging approach (CMR plus strain echocardiography) to better characterize LV status in patients with significant VHD, either AS (a paradigm of LV pressure overload) or MR (a paradigm of LV volume overload).
So far 71 patients have been recruited, and 34 have completed the 1-year follow-up visit.
(MATRIX)
Principal investigator: Borja Ibáñez
ERC Consolidator Grant#819775
The MATRIX Project aims to develop new and innovative treatments for the cardiotoxicity associated with some cancer treatments. MATRIX will be jointly run by the CNIC and Fundación Jiménez Díaz (FJD) University Hospital within a collaborative framework established in 2015 to study myocardial diseases.
Great advances in the treatment of cancer—a disease with 4 million new diagnoses every year in Europe—sometimes come with a 'toll' to pay in the form of major adverse effects. One of the most common adverse effects is myocardial toxicity, which affects up to 25% of patients treated with the common anticancer drugs anthracyclines or trastuzumab. The cardiotoxic effects of these drugs can be very serious and condemn the cancer survivor to chronic heart failure or even death from this complication.
Cancer treatment-induced cardiotoxicity (CTiCT) can result in severe heart failure. The trade-off between cancer and chronic heart failure places an immense personal burden on patients, with physical and psychological consequences. Current therapies for CTiCT are suboptimal, featuring poor early detection algorithms and nonspecific heart failure treatments. Our recently published results and additional preliminary data indicate that CTiCT is associated with altered mitochondrial dynamics, triggering cardiomyocyte metabolic reprogramming. MATRIX adopts a holistic approach to tackling mitochondrial dysfunction in CTiCT. We propose that early-stage CTiCT could be reverted by metabolic reprogramming to shift mitochondrial substrate utilization. By refining a novel imaging-based algorithm recently developed by our group, we will achieve very early detection of myocardial damage in patients treated with commonly prescribed anticancer drugs, long before widely used clinical parameters become abnormal. Such early detection, not available currently, is crucial for early therapeutic intervention. We also hypothesize that in end-stage CTiCT, mitochondrial dysfunction has passed a no-return point, and the failing heart will only be rescued by a strategy to replenish the myocardium with fresh healthy mitochondria. This can be achieved with the radical new therapeutic option of in-vivo mitochondrial transplantation. The MATRIX project has broad translational potential, including a new therapeutic approach to a clinically relevant condition, the development of technology for early diagnosis, and advances in knowledge of basic disease mechanisms.
Patient recruitment began in 2020, and by February 2024 we had already hosted 50 participants.
(MYOCARDITIS-CNIC)
Principal Investigator: Mª Pilar Martín Fernández
Co-Principal investigator: Domingo Pascual Figar
Acute myocarditis is difficult to diagnose because of its varied clinical presentation and the lack of rapid, accessible, and accurate diagnostic methods. The nonspecific manifestations of acute myocarditis include atypical chest pain (suggesting pericarditis or angina), dyspnea, asthenia, palpitations, syncope, and even sudden death or shock. The difficulty in achieving early diagnosis of myocarditis is caused by its varied presentation and the heterogenous and nonspecific findings in the usual tests (ECG, echocardiography, and laboratory tests).
Diagnosis of acute myocarditis typically requires either endomyocardial biopsy, which is invasive, or cardiovascular magnetic resonance imaging, which is not universally available, so there is a clear need for new approaches. Dr. Martín Fernández’s group has identified a novel microRNA in mice and humans with myocarditis; the team’s research shows that the human homolog (hsa-miR-Chr8:96) can be used to distinguish patients with myocarditis from those with myocardial infarction (N Engl J Med. 2021 May 27;384(21):2014-2027).
In the MYOCARDITIS-CNIC Registry, run by the CNIC in collaboration with Hospital Virgen de la Arrixaca, several Spanish hospitals (including Hospital de la Princesa and Clínica Universitaria de Navarra) will collect clinical data and biological samples from patients attending the emergency department with clinical signs of myocarditis. These data will provide valuable information on the early onset of myocarditis and will help in the validation of early clinical biomarkers. So far, 64 participants have been enrolled.
(PRECOGNITIVE)
Principal investigator: Gonzalo Pizarro Sánchez
Arterial hypertension can damage the cerebral vascular system, even when blood pressure values are normalized. Current treatments are aimed at controlling blood pressure and avoiding damage to target organs, such as the brain. Thirty years ago, remote ischemic preconditioning (RIPC) was shown to protect organs such as the heart and brain in animal models, and the procedure has subsequently been used in human patients. RIPC consists of inflating and deflating a tension cuff on the arm through 4 cycles of 5 minutes each. The ischemia generated in the arm can protect distant organs, such as the brain, against future ischemic episodes. Our group has made important contributions in this area, and our recent studies show that RIPC can improve cognitive performance and cerebral vascular function in patients with dementia of vascular origin.
The PRECOGNITIVE study is a proof-of-concept randomized trial in which 45 women with hypertension and evidence of target organ involvement (such as left ventricular hypertrophy) will be randomized into 3 groups. Patients in the RIPC group will receive RIPC (blood pressure increased by 20 mmHg above their systolic blood pressure). The RIPC-Sham group will undergo the same procedure, but the cuff will not be inflated enough to induce ischemia (50 mmHg). The control group participants will not undergo cuff therapy.
The goal is to determine if RIPC has a significant effect on the cerebral vasculature in patients with hypertension without significant cognitive impairment. The effect of the treatment will be assessed through comprehensive neurocognitive tests and noninvasive imaging tests such as echocardiography, noncontrast brain magnetic resonance imaging, and trans-cranial Doppler ultrasound.
By the end of 2023 we had recruited 12 patients.
(MACADAMIA)
Principal investigator: Borja Ibáñez
Heart failure (HF) is one of the main health problems in contemporary societies and a major burden on healthcare resources. In order to develop new therapies, it is crucial to identify new mechanisms involved in the development and maintenance of HF.
The heart is the most energy-consuming organ in the body by weight. The primary energy source for the heart under physiological conditions is beta-oxidation of fatty acids, which generates approximately 60% of the total ATP consumed by the heart. The second energy source is carbohydrate metabolism via the Krebs cycle, while other nutrients such as amino acids contribute less than 1% of cardiac energy production.
In the altered physiological conditions of HF, there is a shift in nutrient consumption by the cardiac muscle, which begins to consume glucose instead of fatty acids, making carbohydrates the main energy substrate. This change is known as the "metabolic switch." Initially, this metabolic switch was considered a protective defense mechanism rather than a deleterious effect. However, recent data from animal and human models indicate that glucose metabolism produces 4-5 times less ATP than that of fatty acids, indicating that this metabolic switch, far from being beneficial, is harmful and contributes to the drop in cardiac contractile capacity.
Our group has demonstrated that the metabolic switch in HF secondary to idiopathic dilated cardiomyopathy (IDCM) is involved in the deterioration of ventricular function. We initially demonstrated this in a mouse model, where a diet rich in fatty acids was able to reverse the metabolic switch and the IDCM phenotype. This ability of a fatty diet to reverse deteriorated ventricular function in IDCM is also seen in pigs, which have a similar metabolism to humans.
The first step before performing a clinical trial in patients with IDCM is to study the incidence of the metabolic switch in this patient group. This is the goal of the MACADAMIA study. MACADAMIA is an observational study of a small number of patients diagnosed with IDCM. The study aims to characterize this population, without any intervention, using cardiac imaging techniques, including transthoracic ultrasound (TTE, including myocardial strain), cardiac magnetic resonance (CMR), and a metabolic study by positron emission tomography/computed tomography (PET/CT) using the radiotracer 18FDG.
By February 2024 we had recruited 28 patients. Our medium–long-term goal is to conduct a clinical trial in IDCM patients in whom these imaging techniques demonstrate a metabolic switch. These patients will be randomized to receive a diet rich in fatty acids or a normal diet, and we will assess changes in cardiac function (by CMR) and cardiac metabolism (by PET/CT) as a function of this dietary intervention
(ATTRACKING CNIC)
Principal Investigator: Pablo García-Pavía
Tafamidis is a drug used to treat transthyretin cardiac amyloidosis (ATTR-CM), a rare, life-threatening disease resulting from the deposition of transthyretin amyloid fibrils in the heart. The effectiveness of Tafamidis has been demonstrated in clinical trials showing a reduction in mortality and cardiovascular hospitalizations in patients with ATTR-CM, and Tafamidis was recently marketed in Spain. However, clinical trials can have biases, and trial results are not always comparable to those obtained in real-world clinical practice. Crucially, improvements in diagnosis mean that ATTR-CM is now diagnosed earlier than in the past, and this has had the effect of altering the patient profile and improving prognosis compared with the study population in the clinical trial that ushered in the authorization of this medication. There is thus uncertainty about the effect of Tafamidis on patients with currently diagnosed ATTR-CM, and the aim of ATTRACKING CNIC is to evaluate the effectiveness and safety of Tafamidis in an unselected contemporary cohort of patients with this disease.
Prospective multicenter non-randomized study of an unselected cohort of patients diagnosed with ATTR-CM and initiating daily treatment with 61 mg Tafamidis.
At the end of 2023 we were finalizing contracts with 10 hospitals in preparation for the beginning of the registry early in 2024.
(TAILOR-AF)
Principal Investigator: David Filgueiras
Co-Promoters: Centro Nacional de Investigaciones Cardiovasculares / Hospital Universitario Clínico San Carlos
Pulmonary vein isolation (PVI) is considered the cornerstone of catheter ablation in patients with persistent atrial fibrillation (AF). However, the results in patients with persistent AF are suboptimal, with high recurrence rates after a single PVI procedure. In current guidelines for AF ablation in patients with persistent AF, an AF-free rate after 12 months without antiarrhythmic drugs of just 40% is considered acceptable, illustrating the difficulty of rhythm control in this type of arrhythmia.
Our group recently developed a computational tool that enables interventional electrophysiologists to identify specific atrial ‘driver regions’ during AF that are associated with long-term perpetuation of the arrhythmia. Using a conventional electroanatomic mapping system and multielectrode catheters, these regions can be identified with novel signal processing algorithms that have been made available to the scientific community (Quintanilla JG et al. Circ Res. 2019;125:609-27). The algorithms use individual atrial signals at each of the atrial mapping locations and provide an automatic and accurate analysis of frequency and amplitude modulations (iFM and iAM) that are present during the fibrillatory activity of the atria. This analysis enables localization of the footprint of rotational activity and determination of which activations drive persistent AF (the leading drivers).
The main objective of this study is to identify (through iAM/iFM maps) and ablate the leading drivers of AF in patients with symptomatic recurrences of persistent AF despite having undergone 2 or more PVI procedures. As secondary objectives, the study analyzes blood biomarkers, atrial imaging parameters, and phenotypic parameters in the surface electrocardiogram associated with advanced stages of atrial remodeling. In patients undergoing minimally invasive thoracoscopy-guided ablation of leading drivers, we also take tissue samples of left atrial appendage tissue to further analyze the underlying molecular mechanisms associated with AF maintenance. By the end of 2023, 15 patients had been included.
(SIR-CVT)
Principal Investigators: Borja Ibáñez and Pilar Martín
Co-Promoters: Centro Nacional de Investigaciones Cardiovasculares / Sociedad Española de Cardiología / Sociedad Española de Oncología Médica
SIR-CVT is a non-interventional study with 2 primary objectives: to evaluate risk factors and daily practice management of cardiovascular toxicity in patients with solid organ cancer receiving immune checkpoint inhibitors (ICI) for approved indications, and to validate the human homolog of miR-721 as a biomarker for the early diagnosis of immunotherapy-induced myocarditis in these patients.
The study will also address the following secondary objectives:
The study consists of a baseline visit, and patients will be treated according to routine clinical protocols, including the frequency of follow-up visits. Patients will be followed up until death, loss-to-follow-up, of the final visit 12 months after enrollment. The information collected will be used exclusively for the purposes of the study.
By February 2024, 3 patients had been included and had undergone cardiac magnetic resonance and ultrasound imaging studies at the CNIC.
The ‘guardian of the genome’ protects against cardiovascular disease
A team at the CNIC led by Dr. Jose J. Fuster, working in collaboration with institutes in the USA, has demonstrated that acquired mutations in the gene encoding the protein p53 contribute to the development of atherosclerotic cardiovascular disease. Known as the ‘guardian of the genome’, p53 helps to maintain the integrity of the hereditary material inside cells by regulating multiple cell functions in response to cellular stresses.
Zekavat SM, Viana-Huete V, Matesanz N, Jorshery SD, Zuriaga MA, Uddin MM, Trinder M, Paruchuri K, Zorita V, Ferrer-Pérez A, Amorós-Pérez M, Kunderfranco P, Carriero R, Greco CM, Aroca-Crevillen A, Hidalgo A, Damrauer SM, Ballantyne CM, Niroula A, Gibson CJ, Pirruccello J, Griffin G, Ebert BL, Libby P, Fuster V, Zhao H, Ghassemi M, Natarajan P, Bick AG, Fuster JJ, Klarin D. TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease. Nat Cardiovasc Res. 2023 Jan 16;2:144-158. https://doi.org/10.1038/s44161-022-00206-6
CNIC scientists identify a new therapeutic target in macrophages for the treatment of obesity-related diseases
A team at the CNIC has discovered that the metabolic requirements of macrophages differ depending on the organ in which they reside. In other words, these cells adapt to the needs of the organ in which they are located. The discovery “gives us a better understanding of how macrophages regulate their metabolism according to the organ in which they reside. Our results reveal a vulnerability of macrophages that contributes to chronic inflammatory diseases and could be exploited for the treatment of conditions associated with obesity and metabolic syndrome, such as cardiovascular disease", said study leader Dr. David Sancho, who heads the CNIC Immunobiology group.
Wculek SK, Heras-Murillo I, Mastrangelo A, Mañanes D, Galán M, Miguel V, Curtabbi A, Barbas C, Chandel NS, Enríquez JA, Lamas S, Sancho D. Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis. Immunity. 2023 Mar 14;56(3):516-530.e9. https://doi.org/10.1016/j.immuni.2023.01.011
Imaging the adolescent heart
Magnetic resonance imaging (MRI) has allowed scientists at the CNIC, led by Dr. Rodrigo Fernández-Jiménez, to produce an accurate picture of the healthy heart in adolescence. Using this advanced technology, the research team was able to determine reference values for anatomical and functional parameters in the heart during adolescence. This information has direct implications for clinical practice. “Magnetic resonance imaging has become a very important method for studying the heart because it avoids exposing patients to radiation and provides more information, and with greater precision, than ultrasound, currently the most frequently used cardiac imaging technique”, said CNIC General Director Dr. Valentín Fuster, a co-author on the study.
Real C, Párraga R, Pizarro G, García-Lunar I, González-Calvo E, Martínez-Gómez J, Sánchez-González J, Sampedro P, Sanmamed I, De Miguel M, De Cos-Gandoy A, Bodega P, Ibanez B, Santos-Beneit G, Fuster V, Fernández-Jiménez R. Magnetic resonance imaging reference values for cardiac morphology, function and tissue composition in adolescents. EClinicalMedicine. 2023 Mar 3;57:101885. https://doi.org/10.1016/j.eclinm.2023.101885
High-dose anticoagulation can reduce the need for intubation and improve survival of hospitalized Covid-19 patients
Compared with standard low-dose anticoagulation, high-dose anticoagulation can reduce deaths by 30 percent and intubations by 25 percent among hospitalized Covid-19 patients who are not critically ill. These are the significant findings from the large-scale international “FREEDOM” trial, led by Valentín Fuster, CNIC General Director, President of Mount Sinai Fuster Heart Hospital, and Physician-in-Chief at Mount Sinai Hospital. The study results were announced at the American College of Cardiology Scientific Sessions, held in partnership with the World Congress of Cardiology in New Orleans (USA), and simultaneously published in the Journal of the American College of Cardiology (JACC).
Stone GW, Farkouh ME, Lala A, Tinuoye E, Dressler O, Moreno PR, Palacios IF, Goodman SG, Esper RB, Abizaid A, Varade D, Betancur JF, Ricalde A, Payro G, Castellano JM, Hung IFN, Nadkarni GN, Giustino G, Godoy LC, Feinman J, Camaj A, Bienstock SW, Furtado RHM, Granada C, Bustamante J, Peyra C, Contreras J, Owen R, Bhatt DL, Pocock SJ, Fuster V; FREEDOM COVID Anticoagulation Strategy Randomized Trial Investigators. Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2023 May 9;81(18):1747-1762. https://doi.org/10.1016/j.jacc.2023.02.041
A Spanish team presents the first pharmacological treatment able to improve cardiac function in stiff-heart syndrome
The results of this study promise to radically alter the prospects of patients with stiff-heart syndrome. The study was led by Dr. Pablo García-Pavía, who heads the Inherited Cardiomyopathies group at the CNIC and the Inherited Cardiac Diseases Section at Hospital Universitario Puerta de Hierro. Coinciding with the publication of the study, Dr. Pablo García-Pavía presented the results of the first clinical trial of an amyloid-removing drug for the treatment of cardiac amyloidosis. The initial results of the trial, which was coordinated by Dr. García-Pavía and included 40 patients in France, the Netherlands, Germany, and Spain, show that the new drug is safe and appears to reduce the amount of amyloid protein deposited in the heart. Developed by the Swiss company Neurimmune, the new medication is an antibody that binds to transthyretin amyloid protein. The antibody was first isolated from memory B cells obtained from healthy elderly individuals.
Garcia-Pavia P, Aus dem Siepen F, Donal E, Lairez O, van der Meer P, Kristen AV, Mercuri MF, Michalon A, Frost RJA, Grimm J, Nitsch RM, Hock C, Kahr PC, Damy T. Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. N Engl J Med. 2023 Jul 20;389(3):239-250. https://doi.org/10.1056/NEJMoa2303765
GLA, the fatty acid that makes the heart function properly after birth
A study conducted in mice and led by Dr. Mercedes Ricote at the CNIC has revealed that maternal milk provides an essential signal that triggers the maturation of heart metabolism after birth, allowing the neonatal heart to function correctly and ensuring postnatal survival. The study shows that the fatty acid gamma-linolenic acid (GLA), present in breast milk, binds to the retinoid X receptor (RXR) protein found in heart cells. RXR acts as a nutritional sensor of lipids and vitamin A derivatives, altering gene expression and influencing biological functions such as immunity, cell differentiation, and metabolism. Once activated by maternal GLA, RXR initiates genetic programs that equip mitochondria—the energy centers of the cell—with the enzymes and other proteins they need to start consuming lipids, the primary source of energy in the mature heart.
Paredes A, Justo-Méndez R, Jiménez-Blasco D, Núñez V, Calero I, Villalba-Orero M, Alegre-Martí A, Fischer T, Gradillas A, Sant'Anna VAR, Were F, Huang Z, Hernansanz-Agustín P, Contreras C, Martínez F, Camafeita E, Vázquez J, Ruiz-Cabello J, Area-Gómez E, Sánchez-Cabo F, Treuter E, Bolaños JP, Estébanez-Perpiñá E, Rupérez FJ, Barbas C, Enríquez JA, Ricote M. γ-Linolenic acid in maternal milk drives cardiac metabolic maturation. Nature. 2023 Jun;618(7964):365-373. https://doi.org/10.1038/s41586-023-06068-7
Scientists identify how some angiogenic drugs used to treat heart disease and cancer cause vascular disease
Research led by Dr. Rui Benedito at the CNIC has demonstrated that most of the transcriptional changes and angiogenic cell states elicited by targeting Dll4 correlate with, but do not cause, vascular pathophysiology. Therefore, vascular neoplasms are not the cause of the previously reported anti-Dll4 antibody toxicity.
Fernández-Chacón M, Mühleder S, Regano A, Garcia-Ortega L, Rocha SF, Torroja C, Sanchez-Muñoz MS, Lytvyn M, Casquero-Garcia V, De Andrés-Laguillo M, Muhl L, Orlich MM, Gaengel K, Camafeita E, Vázquez J, Benguría A, Iruela-Arispe ML, Dopazo A, Sánchez-Cabo F, Carter H, Benedito R. Incongruence between transcriptional and vascular pathophysiological cell states. Nat Cardiovasc Res. 2023 May 29;2:2023530-549. https://doi.org/10.1038/s44161-023-00272-4
Atherosclerosis accelerates aging
Atherosclerosis—the much-feared ‘hardening’ of our arteries—impacts our health long before the appearance of symptomatic cardiovascular disease. A new study by a team at the CNIC shows that atherosclerosis at subclinical stages accelerates the aging process. Lead author and CNIC General Director Dr. Valentín Fuster emphasized that the results underline the benefits of reducing inflammation by adopting a healthy lifestyle (healthy diet, regular physical activity, etc.) or taking specific medication, such as cholesterol-lowering statins, that can block, or at least slow, the transition from the subclinical phase of atherosclerosis to the appearance of severe cerebrovascular events, like myocardial infarction or stroke.
Sánchez-Cabo F, Fuster V, Silla-Castro JC, González G, Lorenzo-Vivas E, Alvarez R, Callejas S, Benguría A, Gil E, Núñez E, Oliva B, Mendiguren JM, Cortes-Canteli M, Bueno H, Andrés V, Ordovás JM, Fernández-Friera L, Quesada AJ, Garcia JM, Rossello X, Vázquez J, Dopazo A, Fernández-Ortiz A, Ibáñez B, Fuster JJ, Lara-Pezzi E. Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study. Eur Heart J. 2023 Aug 1;44(29):2698-2709. https://doi.org/10.1093/eurheartj/ehad361
Promoting cardiovascular health in adolescents at school: a cluster randomized clinical trial
The journal JAMA Cardiology published the results of a project carried out by the SHE Foundation, the CNIC, and the University of Barcelona and which involved the participation of 1326 adolescents from 24 public secondary schools in Madrid and Barcelona.
The study showed a beneficial impact of a health-promotion educational intervention on health parameters in adolescents, with the impact depending largely on the duration and intensity of the intervention. Unfortunately, this impact was not sustained over time. Although health promotion initiatives in the school setting have become increasingly common in recent years, very few have addressed cardiovascular health in a comprehensive manner, and it is therefore important to continue optimizing school-based interventions in order to define the most effective strategies.
Santos-Beneit G, Fernández-Alvira JM, Tresserra-Rimbau A, Bodega P, de Cos-Gandoy A, de Miguel M, Ramírez-Garza SL, Laveriano-Santos EP, Arancibia-Riveros C, Carral V, Orrit X, Rodríguez C, Carvajal I, Haro D, Peyra C, Martínez-Gómez J, Álvarez-Benavides A, Estruch R, Lamuela-Raventós RM, Fernández-Jiménez R, Fuster V. School-Based Cardiovascular Health Promotion in Adolescents: A Cluster Randomized Clinical Trial. JAMA Cardiol. 2023 Sep 1;8(9):816-824. https://doi.org/10.1001/jamacardio.2023.2231
A new technique improves diagnostic accuracy and personalized therapy for a common arrhythmia
A multidisciplinary and multicenter study led by Dr. David Filgueiras, head of the Advanced Development in Arrhythmia Mechanisms and Therapy group at the CNIC and a cardiologist at Hospital Clínico San Carlos, has led to the development of a new approach to assessing the structural and electrophysiological changes that occur in the hearts of patients with atrial fibrillation, one of the most frequent types of arrhythmia. This new diagnostic approach is based on the simultaneous evaluation of the electrical and mechanical (contractile) activity of the atria during atrial fibrillation.
Enríquez-Vázquez D, Quintanilla JG, García-Escolano A, Couselo-Seijas M, Simón-Chica A, Lee P, Alfonso-Almazán JM, Mahía P, Redondo-Rodríguez A, Modrego J, Ortega-Hernández A, Marcos-Alberca P, Magni R, Calvo E, Gómez-Gordo R, Yan P, La Rosa G, Bustamante-Madrión J, Pérez-García CN, Martín-Sánchez FJ, Calvo D, de la Hera JM, García-Torrent MJ, García-Osuna Á, Ordonez-Llanos J, Vázquez J, Pérez-Villacastín J, Pérez-Castellano N, Loew LM, Sánchez-González J, Gómez-Garre D, Filgueiras-Rama D. Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value. Nat Commun. 2023 Aug 4;14(1):4613. https://doi.org/10.1038/s41467-023-40196-y
The sooner we start controlling cardiovascular risk factors, the better for our brains
Cardiovascular disease and dementia often occur together, but there has been a lack of longitudinal studies in middle-aged people evaluating the impact of atherosclerosis and its risk factors on brain health. Now, research led by Dr. Marta Cortés Canteli at the CNIC provides new data on this relationship and confirms the importance of controlling traditional cardiovascular risk factors, such as hypertension, cholesterol, diabetes, smoking, and sedentary lifestyle not only to protect cardiovascular health, but also to prevent diseases such as Alzheimer's.
Tristão-Pereira C, Fuster V, Oliva B, Moreno-Arciniegas A, Garcia-Lunar I, Perez-Herreras C, Schöll M, Suárez-Calvet M, Moro MA, Garcia-Alvarez A, Fernandez-Ortiz A, Sanchez-Gonzalez J, Zetterberg H, Blennow K, Ibanez B, Gispert JD, Cortes-Canteli M. Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study. Lancet Healthy Longev. 2023 Sep;4(9):e487-e498. https://doi.org/10.1016/S2666-7568(23)00134-4
A new therapy discovered for a heart condition that causes an estimated 20% of sudden deaths among athletes
A CNIC team led by Dr. Juan Bernal has discovered a possible treatment for a disease that causes the death of elite athletes without warning. Arrhythmogenic cardiomyopathy is an incurable disease of the heart muscle that is responsible for an estimated 20% of sudden deaths recorded in professional athletes. While there is still a long way to go to fully define the molecular basis of this disease, the current study identifies a group of mutations in the placophilin-2 protein that are associated with severe contractile problems that respond to treatment with the myosin activator 4-hydroxyacetophenone.
García-Quintáns N, Sacristán S, Márquez-López C, Sánchez-Ramos C, Martinez-de-Benito F, Siniscalco D, González-Guerra A, Camafeita E, Roche-Molina M, Lytvyn M, Morera D, Guillen MI, Sanguino MA, Sanz-Rosa D, Martín-Pérez D, Garcia R, Bernal JA. MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM). Nat Commun. 2023 Oct 13;14(1):6461. https://doi.org/10.1038/s41467-023-41981-5
Spanish scientists identify a key action of dendritic cells in the immune response, with potential applications in vaccine design
This study, led by Dr. Francisco Sánchez-Madrid, provides invaluable information on the mechanisms involved in the body's immune response to pathogens and opens a new avenue for the design of innovative vaccines against future pandemics. The study reveals that the formation of an immune synapse not only activates the participating lymphocyte, as was already known, but also triggers profound changes in postsynaptic dendritic cells.
Calzada-Fraile D, Iborra S, Ramírez-Huesca M, Jorge I, Dotta E, Hernández-García E, Martín-Cófreces N, Nistal-Villán E, Veiga E, Vázquez J, Pasqual G, Sánchez-Madrid F. Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+T cells. Nat Commun. 2023 Oct 25;14(1):6772. https://doi.org/10.1038/s41467-023-42480-3
Obesity, hypertension, and dyslipidemia induce a progressive loss of energy in the heart
According to this new study, altered consumption of energy substrates in the heart due to metabolic risk factors such as obesity, hypertension and dyslipidemia can promote the appearance years later of diseases such as heart failure.
This study was carried out as part of the CNIC-SANTANDER PESA project, run jointly by the CNIC and Banco Santander and begun more than 10 years ago. “PESA is the flagship project of the CNIC, since many of the center’s leading research groups, each with expertise in a specific area of cardiovascular disease, work around the study. Combining the participation of basic and clinical researchers around a large cohort such as PESA is unique in the world”, explained Dr. Valentín Fuster.
Devesa A, Fuster V, Vazirani R, García-Lunar I, Oliva B, España S, Moreno-Arciniegas A, Sanz J, Perez-Herreras C, Bueno H, Lara-Pezzi E, García-Alvarez A, de Vega VM, Fernández-Friera L, Trivieri MG, Fernández-Ortiz A, Rossello X, Sanchez-Gonzalez J, Ibanez B. Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis. Diabetes Care. 2023 Nov 1;46(11):2050-2057. https://doi.org/10.2337/dc23-0871
Key role of the protein Nrg1 in proper heart formation
A team of CNIC researchers led by Dr. José Luis de la Pompa has identified the signaling protein Nrg1 as a key player in the process of heart formation. Nrg1 guides the formation of the trabeculae carneae, muscular columns in the ventricles that are some of the first cardiac structures to develop. Nevertheless, the intricate mechanisms by which Nrg1 operates and its role in heart wall maturation remain an enigma.
Grego-Bessa J, Gómez-Apiñaniz P, Prados B, Gómez MJ, MacGrogan D, de la Pompa JL. Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development. Circ Res. 2023 Nov 10;133(11):927-943. https://doi.org/10.1161/CIRCRESAHA.123.323321
Young people are more vulnerable to the damaging effect of high cholesterol and high blood pressure
According to this CNIC research, young people are more vulnerable to the detrimental effects of two major cardiovascular risk factors: high cholesterol and high blood pressure. Subclinical atherosclerosis often progresses in middle-aged people, especially when LDL-cholesterol levels and blood pressure are elevated, even slightly or moderately. Both the medical community and the general public should be aware that the progression of atherosclerosis can be halted if risk factors are aggressively managed from an early age.
Dr. Valentín Fuster concluded that "screening for subclinical atherosclerosis from an early age, together with aggressive control of risk factors, could help to alleviate the overall burden of cardiovascular disease".
Mendieta G, Pocock S, Mass V, Moreno A, Owen R, García-Lunar I, López-Melgar B, Fuster JJ, Andres V, Pérez-Herreras C, Bueno H, Fernández-Ortiz A, Sanchez-Gonzalez J, García-Alvarez A, Ibáñez B, Fuster V. Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years. J Am Coll Cardiol. 2023 Nov 28;82(22):2069-2083. https://doi.org/10.1016/j.jacc.2023.09.814
A promising therapeutic target for cardiac arrhythmias
A study carried out by the teams of Guadalupe Sabio and José Jalife at the CNIC has discovered a link between the p38γ and p38δ stress kinase signaling pathway and the onset of ventricular fibrillation, a type of cardiac arrhythmia. During an arrhythmic event, the heart rhythm is disturbed, quickens, and becomes irregular, with potentially fatal consequences. This study offers new hope for tackling the disease.
Romero-Becerra R, Cruz FM, Mora A, Lopez JA, Ponce-Balbuena D, Allan A, Ramos-Mondragón R, González-Terán B, León M, Rodríguez ME, Leiva-Vega L, Guerrero-Serna G, Jimenez-Vázquez EN, Filgueiras-Rama D, Vázquez J, Jalife J, Sabio G. p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia. Nature Cardiovascular Research. 2023 Nov 27, (2): 1204–1220. https://doi.org/10.1038/s44161-023-00368-x
Molecular mechanisms discovered that govern critical genes for cardiac valve formation
A CNIC research team led by Dr. José Luis de la Pompa has identified the molecular mechanisms that control the activity of genes involved in both the proper formation of cardiac valves and the prevention of their subsequent calcification. The study demonstrated that cooperation between the NOTCH and the HIPPO signaling pathways is essential for the correct participation of the endocardium in valve formation.
Luna-Zurita L, Flores-Garza BG, Grivas D, Siguero-Álvarez M, de la Pompa JL. Cooperative Response to Endocardial Notch Reveals Interaction With Hippo Pathway. Circ Res. 2023 Dec 8;133(12):1022-1039. https://doi.org/10.1161/CIRCRESAHA.123.323474
CNIC research identifies mutations that underlie one of the most frequent congenital heart defects
Bicuspid aortic valve is the most frequent congenital heart defect in humans, affecting between 1% and 2% of adults. This defect often causes valve stenosis and endocarditis and is associated with early calcification of the aortic valve. The only treatment currently available is surgical valve replacement, but the results of this new study led by Dr. José Luis de la Pompa at the CNIC could change this situation. By identifying the mutations underlying this defect, the new study points the way to the future design of pharmacological and alternative therapies.
Grego-Bessa J, Gómez-Apiñaniz P, Prados B, Gómez MJ, MacGrogan D, de la Pompa JL. Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development. Circ Res. 2023 Nov 10;133(11):927-943. https://doi.org/10.1161/CIRCRESAHA.123.323321
1 - VISITING SCIENTISTS AT THE CNIC
Spain’s growing international profile in scientific research makes it an increasingly attractive destination for visiting scientists from all over the world.
The Jesús Serra Foundation (now Fundación Occident) and the CNIC have worked together since 2013 to bring visiting scientists to the CNIC within the framework of the Visiting Researchers Program.
This program supports visits by international scientists to Spanish research centers, with the aim of building strong inter-institutional bonds and promoting new lines of research.
Foundation President Federico Halpern explained that an important aim of the Program is to “ensure the continuity of research projects that might otherwise be paralyzed due to lack of resources.”
In September 2023, two senior scientists, Dr. Mark Hlatky (Stanford University) and Dr. Carlos Morillo (Calgary University), began one-year collaborative visits at the CNIC in the groups of Dr. Borja Ibáñez and Inés García Lunar (Mark Hlatky) and Dr. José Jalife and David Filgueiras (Carlos Morillo). CNIC General Director Dr. Valentín Fuster said that “The Visiting Researchers Program is an especially good match with the CNIC’s core aim to attract international talented scientists in order to achieve excellence in cardiovascular research. I am sure that great things will come out of this collaboration”.
The CNIC participated last year in the EUCYS through special award consisting of a three-day stay at the CNIC for a scientist with an individual biomedicine project and who, according to the jury, would benefit most from the visit. The award covered travel, meals, and accommodation.
The 2022 winner, Lucia Cengelova, from Czech Republic, visited the CNIC in June 2023 to learn about the Center's projects directly from our researchers. Her stay was mentored by Dr. Mª Ángeles Moro, who has for several years been a member of the committee responsible for selecting the winning projects for years. Lucia Cengelova also learned about the infrastructure and technology available at the Center and how these are used to address and solve the challenges of cardiovascular health research.
The 2023 winner, Sachi N. Premaratne, from Sweden, will complete her visit to the Centre in 2024.
These visits were financed with CNIC Severo Ochoa Grant CEX2020-001041-S.
2 - AWARDS and HONORS
Dr. Valentín Fuster, General Director of the CNIC, received the Gold Medal for Scientific Merit, awarded by the City Council of Barcelona. The city council awarded Dr. Fuster the medal in recognition of his scientific career, his dedication to research, and his commitment to society.
Dr. Francisco Sánchez-Madrid, Head of the CNIC Intercellular Communication in the Inflammatory Response Group, was awarded the 2023 Robert Koch Prize alongside the researcher Timothy Springer for their important joint research in Immunology. Both scientists were pioneers in discovering the importance of cell adhesion molecules for the function of immune cells. This major finding opened up new possibilities for the treatment of immune diseases with monoclonal antibodies. Dr. Sánchez-Madrid is also Head of the Immunology Service at La Princesa University Hospital, Director of the IIS Princesa Healthcare Research Institute and Professor in Immunology at the Autonomous University of Madrid.
Dra. Guadalupe Sabio Buzo received the XXVII award and Dr. David Sancho the XXVIII award for research in molecular biology from the Fundación Carmen y Severo Ochoa, in recognition of their brilliant careers in this field.
The prize is awarded for the research work of scientists in the field of molecular biology who mainly conduct their research in Spain, and recognizes work undertaken in the last five years.
CNIC researcher Dr. Rodrigo Fernández Jiménez was awarded the Gabriella Morreale National Research Award for Young Researchers in the area of Medicine and Health Sciences. The National Research Awards recognize the merit of Spanish researchers who are conducting outstanding work in scientific fields of international relevance and who has made a significant contribution to the advance of scientific knowledge and human progress.
The AstraZeneca Foundation awarded Dr. Valentín Fuster the Honorary Award for Excellence in Scientific Career. The award recognizes the careers of scientists who have contributed to the generation of knowledge and advances in their specialty. The 2023 award was bestowed on Dr. Valentín Fuster, Director General of the CNIC and President of the Cardiovascular Institute and Physician-in-Chief at Mount Sinai Medical Center in New York, for his contributions to cardiovascular medicine, which have significantly improved the treatment of patients with heart disease.
Mount Sinai Hospital changed the name of its Cardiovascular Hospital to the Mount Sinai Fuster Heart Hospital in honor of Dr. Valentín Fuster, CNIC Director General. The name change acknowledges Dr. Fuster’s immeasurable impact on the field of cardiology and his leadership at Mount Sinai.
CNIC General Director Dr. Valentín Fuster is one of the most influential people in health care in Spain, according to the Forbes list of the 25 most influential people in Spanish healthcare, one of the most respected list of its type in the world according to the WHO and other international organizations. Dr. Fuster holds the second position, and he is not the only representative of the CNIC on the list; Dr. Borja Ibáñez, CNIC’s Scientific Director and a cardiologist at Hospital Fundación Jiménez Díaz, is also included among the 25 leading health care professionals in Spain.
CNIC researcher Cintia Folgueira Cobos received the prize from the European Association for the Study of Obesity and the Novo Nordisk Foundation in the category of Basic Science for her excellence and commitment. The award provides of approximately €40,000 in funding and will support participation in the European Congress on Obesity.
CNIC researcher Dr. Ana Paredes was awarded the 2023 Birnstiel International Award for her doctoral research on cardiac metabolism, supervised by Dr. Mercedes Ricote.She obtained her doctorate degree from the Autonomous University of Madrid on February 3, 2023, with her thesis conducted in the Nuclear Receptor Signaling Group at CNIC, titled “Understanding the role of Retinoid X Receptors in cardiac homeostasis: from transcription to physiology”.
Researcher Anabel Díaz-Guerra received an award of €88,000 from the Spanish Association Against Cancer (AECC) in Madrid to contribute to her predoctoral work in the Translational Laboratory for Cardiovascular Imaging and Therapy headed by Dr. Borja Ibáñez, scientific director of CNIC.
The project explores the consequences that cancer treatments can have on the hearts of survivors, with the ultimate goal of developing innovative treatments to reduce associated cardiac toxicity.
3 - GRANTS
This European Union supported COFUND postdoctoral fellowship program at the CNIC is open to excellent researchers of any nationality seeking to conduct research on the heart, the brain and the connection between these organs, a topic of the utmost medical and social importance. The program is co-funded by Horizon Europe (Marie Skłodowska-Curie grant agreement No GA-101126521: €1.719.360) and the Severo Ochoa grant. The CNIC will incorporate 12 international postdoctoral researchers in 2024 and 2025, and 24 international partners from different sectors will contribute translational elements. The selection and recruitment process will follow the European Charter and Code for Researchers and the Code of Conduct for the Recruitment of Researchers and will be merit based, independent and transparent. Applications will be assessed by external evaluators according to principles of merit and scientific excellence. Principal investigators: Enrique Lara Pezzi, Maria A Moro, Inga Dreville.
EU4Health
Jacardi: Joint action on cardiovascular diseases and diabetes
Principal investigators: Hector Bueno, Fátima Sánchez Cabo and Fátima Lois (Partner). Amount granted. € 846.627
ABCardionostic: Human Antibody-enabled Cardiovascular Personalized Theranosis
Principal investigator: Carlos Pérez Medina (partner). Amount granted. € 503.065
DCM-NEX: Enabling advances in diagnosis, patient stratification and treatment for dilated cardiomyopathy patients and families
Principal investigator: Enrique Lara Pezzia (partner). Amount granted. € 461.000
4 - SCIENTIFIC EVENTS
SCIENTIFIC COMMITTEE
This event of the Spanish Proteomics Society (SEProt) was held at the CNIC in February 2023. The organizing committee included CNIC predoctoral researchers from the laboratory of Jesús Vázquez, head of the CNIC Proteomics Group Unit.
The program included sessions on biomedical proteomics, bioinformatics, and translational modifications and systems biology The participants were SEProt members, non-member using proteomics or other related omics technologies as metabolomics, and other interested Spanish or international researchers.
CNIC PhDay 2023: ‘AI-Magining the Future’, was held at the CNIC on 1 December.
The CNIC PhDay is an annual conference organised by pre- and postdoctoral researchers from the Spanish National Centre for Cardiovascular Research (CNIC), for pre- and postdoctoral researchers from CNIC and other centres. Its aim is to explore topics related to professional development in scientific careers from different perspectives, to promote the exchange of new ideas and to establish contacts.
The CNIC PhDay 2023 edition was attended by 15 speakers and 200 participants. The focus of the event was to address what is the contribution of science and medicine in biotechnological progress and how technology also contributes significantly in our daily life in science and in the clinical aspect. Also the event addressed a very important issue, the role of artificial intelligence in science and everyday life. In addition, workshops in the program helped predoctoral participants to successfully complete their theses.
5 - OUTREACH ACTIVITIES
On 8th March, CNIC held an event designed to introduce young people to 4 of the Centre’s women who are part of the PESA HEALTH CNIC-Santander project. The goal of the CNIC video aimed at secondary, pre-university and vocational training students is to introduce young people to the experience, talent and profiles needed to work in this area of interesting scientific challenge.
The video is part of the initiative, #EmpresasQueInspiran of the Fundación Bertelsmann that aims to awaken vocation in the field of science and technology.
As previous years, CNIC participated in the European's Researchers' Night and Science and Madrid Innovation Week with several activities including DNA Adventure: Explore and Edit, Researching Rare Diseases: Challenges and Opportunities and the the RESILIENCE Workshop and Lab Visit: Surviving Cancer with a Strong Heart.
6 - SOCIAL & CNIC
There's no better way to take care of our cardiovascular health than lead by example. That’s why a group of CNIC researchers participated in the 14th Popular Heart Race organized by the Spanish Heart Foundation. Promoting cardiovascular health through such initiatives is a great idea because it introduces the concept of health to the wider community. #MueveteporCNIC
Training is one of the CNIC’s core activities, and the Center has devised a comprehensive training plan, the CNIC-Joven Training Plan. This global plan includes programs for participants at all levels, from high-school students to postdoctoral researchers and MDs. The CNIC-Joven Training Plan aims to fulfill the personal goal of Valentín Fuster “to attract and train the brightest young people from the earliest ages to create a pool of researchers of excellence in the field of cardiovascular research.”
ACERCATE PROGRAM
The Acércate Program offers the highest-achieving senior high school students in the natural and health sciences an opportunity to experience life as biomedical researchers through a national competitive selection process. The program aims to awaken and strengthen their interest in a career in biomedical research.
Participants spend two weeks at the CNIC, where they learn modern biomedical research techniques, conduct supervised experiments, operate sophisticated scientific equipment, and present their findings, all under the guidance of CNIC researchers.
Fellowships in 2023: 8
4º ESO – CNIC
The Madrid Directorate General of Secondary Education launched the 4th Year ESO + Company Program in the 2008-2009 academic year. This program, classified as a complementary activity, is being adopted voluntarily by an increasing number of schools.
Its aim is to bridge the gap between the educational system and the labor market by providing educational placements in companies and institutions. This initiative helps young people become better prepared to make informed decisions about their academic and professional futures, motivating them and equipping them with essential skills.
The CNIC collaborates with the 4ºESO-CNIC Program every year. Last year, 11 life-science students from six schools spent four full days at the CNIC laboratories exploring possible scientific careers.
Internships are offered to university students in the following programs:
The Cicerone Program is open to advanced undergraduate students and Master’s students in biomedicine-related disciplines. Participants extend their scientific training through hands-on experience of laboratory-based biomedical research during the summer recess. In addition to carrying out a supervised research project, the students attend CNIC seminars and workshops. The aim of the program is to give students first-hand knowledge of biomedical research so that they can make informed choices about pursuing a scientific career.
Fellowships in 2023: 31
The CNIC offers practical training in cardiovascular research to visiting undergraduate students through formal collaborative agreements with Spanish and international universities.
In 2023, 27 students from the following universities completed internships at the CNIC related to their final degree thesis dissertation (TFG) under the guidance of a CNIC supervisor:
In addition, 18 students from Spanish and international universities completed other types of university internships at the Center during 2023 under the guidance of a CNIC supervisor:
These grants provide funding for students studying for a master’s degree at a Spanish university to carry out their experimental project (TFM) in a CNIC laboratory.
Fellowships in 2023: 12
Other Master’s Student Internships
In 2023, another 21 students from the following universities worked on their TFM under the guidance of a CNIC supervisor:
The Predoctoral Program provides a unified framework for all CNIC researchers who are working toward a doctoral degree. All predoctoral researchers are signed up to this program, irrespective of their funding source.
The aims of the program are to ensure uniform quality of predoctoral training at the CNIC and further to ensure fair and equal access of predoctoral researchers to training opportunities.
The Program schedules regular meetings between the predoctoral fellow and his or her thesis committee, composed of the thesis director, another CNIC group leader, and an external expert.
Graduate students at the CNIC awarded a PhD degree in 2023: 35
Graduate students studying for a PhD degree at the CNIC in 2023: 115
The CNIC PhD Office is the forum for scientific support, guidance, and growth of all PhD students enrolled on the CNIC Predoctoral Program, independently of their university affiliation or funding source. The office is coordinated by a group leader appointed by the CNIC management.
This office also includes two permanent members (Head of the CNIC Scientific Management office and a manager of the Research Office), and one senior and one junior PhD student, who are elected by the CNIC’s PhD students.
In 2023, a two-day course was organized for 24 advanced predoctoral students, led by professional experts, on how to write successful grant and funding applications. The course was divided into four interactive, in-person modules:
This postgraduate course is run by the CNIC as part of the Universidad Autónoma de Madrid (UAM) Molecular Biosciences Master’s Program. This optional module provides a broad overview of cardiovascular biology, including perspectives from basic, clinical, and translational research.
Attendants on this course are enrolled UAM Master’s students, CNIC predoctoral researchers, and participants in the Res@CNIC SEC Program (see below).
UAM Master’s students in 2023: 12
The Res@CNIC-SEC Program (in collaboration with the Spanish Society of Cardiology, SEC) offers resident medical interns the opportunity during the first years of their specialization period to learn about the latest techniques in cardiovascular research being used in the CNIC laboratories, under the guidance of a CNIC scientist. Residents participating in RES@CNIC also receive training in theoretical aspects of cardiovascular research through an expert-led taught module. The Program also seeks to create links and collaborations so that on conclusion of their MIR specialization period, these professionals will have the chance to undertake research projects in their respective Hospitals in partnership with CNIC scientists.
Participants in 2023: 25 from the following hospitals:
In 2023, this program attracted 15 technical school students studying “Pathological Anatomy and Cytodiagnostics”, “Clinical and Biomedical Laboraxtory”, and “Diagnostic Imaging and Nuclear Medicine” to gain practical experience in the CNIC’s laboratories over a three-month period.
The CNIC has collaborative agreements for this kind of internship with 19 technical training educational centers and with the two DUAL Centers in Madrid offering biomedicine-related courses: Instituto de Educación Secundaria Moratalaz for “Clinical and Biomedical Laboratory” and Instituto de Educación Secundaria San Juan de la Cruz for “Diagnostic Imaging and Nuclear Medicine”.
The aim of this Program (also organized in collaboration with the SEC) is to foster high-quality translational research in the cardiovascular area in Spanish National Health System centers through training programs providing theory and practical training for cardiologists with a research vocation. One trainee is selected every two years year.
Specific aims:
a) To create the figure of the cardiologist researcher by providing high-quality training in clinical research methods, including statistical analysis and the latest basic research techniques used in cardiovascular biomedicine, as well as opportunities to explore any clinical area of cardiology in greater depth (sub-specialization).The program is aimed at cardiologists who aspire to carry out advanced clinical and research work at any center within the Spanish National Health System.
b) International training. The Program offers a period of training toward a Master’s Degree at the London School of Hygiene and Tropical Medicine (90 ECTS).
This course is organized by the CNIC in partnership with the Sociedad Española de Cardiología. The course is aimed at R3, R4, and R5 residents in cardiology and other specialties related to cardiovascular disease, and translational researchers working in the field of cardiology.
Participants receive an overview of the molecular and genetic factors underlying cardiac diseases and gain a current understanding of cardiac physiology through the presentation and discussion of papers authored by CNIC scientists. These sessions are further enriched by contributions from a clinical expert specializing in the topic of each paper.
The XVI edition of this course was held in the CNIC Auditorium on November 24, 2023.
PUBLICATIONS IN WoS
| NUMBER | PERCENTAGE | |
|---|---|---|
| Articles | 243 | 71% |
| Reviews | 32 | 9% |
| OTHER | 67 | 20% |
| TOTAL | 342 |
PUBLICATIONS with Impact Factor Total: 318
| JOURNAL QUALITY | NUMBER | PERCENTAGE |
|---|---|---|
| D1 | 132 | 42% |
| Q1 | 231 | 73% |
| Q2 | 69 | 22% |
| Q3 | 12 | 4% |
| Q4 | 6 | 1% |
| OPEN ACCESS | NUMBER | PERCENTAGE |
|---|---|---|
| All types of OPEN ACCESS | 227 | 71% |
| GOLD OPEN ACCESS | 184 | 58% |
| LEADERSHIP | NUMBER | PERCENTAGE |
|---|---|---|
| First, last or corresponding author | 178 | 56% |
Publications in Top Journals (IF>10)
110(35%)
TOP 3: Publications IN THE TOP THREE JOURNALS WITHIN THEIR CATEGORIES
34(11%)
| AFFILIATION AND COLLABORATION | NUMBER | PERCENTAGE |
|---|---|---|
| CNIC | 11 | 3% |
| National collaboration | 121 | 38% |
| International COLLABORATION | 186 | 58% |
| OTHER IMPACT INDICATORS | NUMBER | PERCENTAGE |
|---|---|---|
| Docs Cited | 192 | 60% |
| Highly Cited Papers* | 13 | 4% |
| Hot PAPERS** | 3 | 1% |
*Highly Cited Papers: Articles that have received enough citations to be ranked in the top 1% in their respective scientific areas, type of document and year of publication.
**Hot Papers: Articles that in the export date have received enough citations to be positioned in the top 0.1% in the respective scientific areas, type of document and year of publication.
List of all CNIC 2023 Publications at: https://www.cnic.es/es/investigacion/publicaciones/resultados?y=2023
Projects, equipment and personnel
| National |
|---|
| 62 Grants |
| €12,699,526.75 |
| International |
|---|
| 11 Grants |
| €2,874,774.98 |
| National |
|---|
| 174 Grants |
| €37.258,004.63 |
| International |
|---|
| 29 Grants |
| €16,564,653.62 |
| 19 | Active Patent families |
| 7 | Patent families Licensed |
| 5 | Priority patent applications during 2023 |
| 57 | New Material Transfer Agreements |
| 14 | New Confidential Disclosure Agreements |
| 2 | New Research Collaboration Agreements |
| women | |
| 237 | 150 |
| MEN | |
(10%)
| men | |
| 23 | 7 |
| WOMEN | |
| MEN | |
| 6 | 5 |
| women | |
(28 From institutions outside Spain; 9 countries)
| women | |
| 139 | 88 |
| MEN | |
AGENCIA ESTATAL DE INVESTIGACIÓN
BOEHRINGER INGELHEIM GMBH
BRIGHTFOCUS FOUNDATION
BRITISH HEART FOUNDATION
COMUNIDAD DE MADRID
DANISH CARDIOVASCULAR ACADEMY
EC-EUROPEAN COMMISSION
EC-EUROPEAN RESEARCH COUNCIL
EUROPEAN FOUNDATION FOR THE STUDY OF DIABETES
FUNDACIÓN BBVA
FUNDACIÓN CARMEN Y SEVERO OCHOA
FUNDACIÓN CIENTIFICA DE LA AECC
FUNDACIÓN ESPAÑOLA DE TROMBOSIS Y HEMOSTASIA
FUNDACIÓN ESPAÑOLA PARA LA CIENCIA Y LA TECNOLOGIA
FUNDACIÓN EUGENIO RODRIGUEZ PASCUAL
FUNDACIÓN LA CAIXA
FUNDACIÓN LA MARATO TV3
FUNDACIÓN RAMON ARECES
INSTITUTO DE SALUD CARLOS III
JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE
LASEXTA Y LA FUNDACIÓN AXA
LEDUCQ FOUNDATION
MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
MINISTERIO DE TRABAJO Y ECONOMÍA SOCIAL
NATIONAL INSTITUTES OF HEALTH
NOVONORDISK
PROGERIA RESEARCH FOUNDATION
SOCIEDAD ESPAÑOLA DE CARDIOLOGIA
SOCIETY FOR ENDOCRINOLOGY
SOCIETY FOR FREE RADICAL RESEARCH - EUROPE
SWEDISH SOCIETY FOR MEDICAL RESEARCH
THE COMPANY OF BIOLOGISTS
THE EUROPEAN ASSOCIATION FOR THE STUDY OF OBESITY
WORLDWIDE CANCER RESEARCH
The Pro CNIC Foundation brings together 11 of the most important Spanish companies and foundations: Acciona, Endesa, the Mapfre Foundation, the Mutua Madrileña Foundation, the Ramón Areces Foundation, the Repsol Foundation, Santander Foundation, Inditex, la Caixa, Prisa, and Telefónica.
This innovative public-private financing formula has allowed the CNIC to reach a very high level of excellence, as recognized in the Severo Ochoa accreditation and other international awards.
© Centro Nacional de Investigaciones Cardiovasculares (F.S.P.), 2023
DL: M-6459-2024
