Author Archive

Dr. Andrés Hidalgo elected a member of the European Molecular Biology Organization – EMBO

Dr. Andrés Hidalgo has been elected a member of the European Molecular Biology Organization (EMBO). EMBO today named the 56 new members who will form part of this organization of more than 1800 leading scientists from Europe and around the world.

With the incorporation of Dr. Hidalgo, there are now six members of the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in EMBO: Dr. José Antonio Enríquez, Dr. Miguel Ángel Del Pozo, Dr. Miguel Torres, Dr. Pura Muñoz and to Dr. Francisco Sánchez Madrid.

EMBO announces that 67 researchers have been elected to its membership. Through this lifelong honour, new EMBO Members and Associate Members are recognized for their outstanding achievements in the life sciences.

“The new EMBO Members and Associate Members are exceptional scientists, who carry out leading research across a variety of fields, ranging from cell biology and cancer to vaccine development and machine learning,” says EMBO Director Fiona Watt. “I am delighted to welcome them to EMBO, and I know that they will enrich the life of the organization immensely.”

Members provide guidance and support for EMBO activities, for example by evaluating funding applications, serving on EMBO Council and committees, or joining the editorial boards of EMBO Press journals. Through their involvement, members help to shape the direction of life sciences, foster the careers of young researchers, and strengthen the research communities in Europe and beyond.

New members are nominated and elected by the existing EMBO Membership. The annual process ensures a broad scope with the flexibility to expand into newly emerging fields in the life sciences.

EMBO will formally welcome the new members at the annual Members’ Meeting in Heidelberg between 26 and 28 October 2022.

EJHF: Spanish scientists combine genetic and imaging data to improve the treatment of dilated cardiomyopathy

Combining a person’s genetic profile with imaging data obtained by cardiac magnetic resonance accurately predicts the prognosis of patients with dilated cardiomyopathy, the most frequent cause of heart failure.

This is the finding of a Spanish study published in the European Journal of Heart  Failure and coordinated by Dr. Pablo García-Pavía, cardiologist at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), and  Hospital Puerta de Hierro Majadahonda in Madrid, and a member of the Spanish research network on cardiovascular disease (CIBERCV). The study is the largest in the world to correlate clinical outcomes with the genetic profiles and cardiac magnetic resonance data of dilated cardiomyopathy patients.

Dilated cardiomyopathy is the most frequent cause of heart disease in young people and the leading cause of heart transplantation in the world. The disease affects 1 person in every 250 of the general population and is characterized by an enlargement of the heart accompanied by a decline in its capacity to pump blood.

Patients with this condition are at high risk of arrhythmias and sudden cardiac death.

The study examined genetic and cardiac magnetic resonance data collected from 600 patients in 20 Spanish hospitals between 2015 and 2020. The investigators demonstrated that a combination of specific genetic traits with the presence of fibrosis detected by cardiac magnetic resonance imaging accurately identifies those patients who will develop malignant arrhythmias or severe complications of heart failure.

Dr. Jesús Gonzalez Mirelis, a cardiologist at Hospital Puerta de Hierro and codirector of the study, explained that there is currently a lack of good prognostic markers for patients with dilated cardiomyopathy. As a result, to prevent sudden death, patients are routinely selected for more aggressive interventions, such as the placement of a defibrillator device, based on the degree of weakening of the heart’s pumping action.

A new study publihed in the European Journal of Heart Failure
presents the largest genetic analysis to date of dilated cardiomyopathy patients monitored longitudinally by cardiac magnetic resonance

The new study shows that classifying patients according to their genetic profile and the presence of fibrosis detected by cardiac magnetic resonance imaging “gives a much more accurate indication of patient risk than the extent of weakening of cardiac pumping capacity, the method used until now; the problem with the current method is that some patients with low-grade cardiac weakening develop complications, whereas others with extensive weakening are stable and don’t develop problems over the long term,” said Dr. García Pavía.

The researchers found that patients lacking genetic alterations and showing no sign of fibrosis had a very good prognosis, with little risk of sudden death irrespective of the weakening of cardiac pumping capacity.

According to the authors, the study opens the way to a more personalized approach to dilated cardiomyopathy, with each patient receiving the most appropriate treatment based on a precise cardiological assessment.

“The findings of this study allow dilated cardiomyopathy patients to be treated according to their specific characteristics and open the way to the application of personalized medicine in this area of cardiology,” concluded Dr. García-Pavía.

The following centers participated in the study: Hospital Universitario Puerta de Hierro, IDIPHISA; CIBER Cardiovascular; Hospital General Universitario Gregorio Marañón; Instituto de Investigación Biomédica de Salamanca (IBSAL)- Complejo Asistencial Universitario de Salamanca; Universidad de Salamanca; Hospital Universitario Virgen de la Arrixaca de Murcia; Hospital Universitari Vall d’Hebron, Vall d’Hebron Instituto de Recerca (VHIR), Universitat Autonoma de Barcelona; Complejo Hospitalario de Navarra; Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña; Universidad de A Coruña;  Complejo Hospitalario Universitario de Cáceres; Hospital Universitario Virgen de la Victoria IBIMA, Málaga; Instituto de Ciencias del Corazón (ICICOR); Hospital Clínico Universitario Valladolid; Hospital General Universitario de Alicante, Instituto de Salud e Investigación BiomédicaHospital Universitario 12 de Octubre, Instituto de Investigación i+12Hospital Clínico, IDIBAPS, Universitat de Barcelona; Instituto de investigación Sanitaria de Santiago; Complexo Hospitalario Universitario de Santiago;  Hospital Universitario Virgen de las Nieves; Hospital Universitario Son Llatzer & IdISBa; Hospital Universitario Virgen del Rocío; Hospital Univesitari Dr. Josep Trueta; Instituto del Corazón & Hospital Universitario Germans Trias, and Universidad Francisco de Vitoria (UFV).

The study was funded by grants from the Instituto de Salud Carlos III with cofunding from the Euroean Regional Development Fund (“A way to build Europe”) and the European Social Fund (“Investing in Your Future”).

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non-ischaemic dilated cardiomyopathy. Jesús G. Mirelis, Luis Escobar-Lopez, Pablo García-Pavía et al.

European Heart Journal: “One change a day makes 365 changes in a year”

Many cardiovascular disorders can be prevented by taking action to reduce risk factors. Making even small behavioral changes and sticking with them over the long term can help to preserve cardiovascular health. This is the conclusion of a study conducted at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and published in the European Heart Journal. The study also demonstrates that the workplace is an ideal setting for programs promoting the adoption of heart-healthy habits and producing major health benefits.

Cardiovascular disease is the number 1 cause of death in the world and represents one of the greatest economic challenges for health systems. The development of cardiovascular disease is strongly influenced by features of modern unhealthy lifestyles such as physical inactivity, poor diet, and alcohol and tobacco consumption.

A few years ago, CNIC General Director Dr. Valentín Fuster launched the TANSNIP project, an international initiative that includes partners in the United States (Icahn School of Medicine at Mount Sinai Hospital in New York and the Framingham study) and Europe (the CNIC and Amsterdam UMC). The goal of TANSNIP is to develop tools for lifestyle improvement based on the use of imaging techniques to detect the presence of atherosclerosis in its early stages, before the appearance of symptoms and events such as heart attack or stroke.

In 2015, the TANSNIP project launched a major intervention to promote a heart-healthy lifestyle in 1000 individuals from the PESA-CNIC-Santander cohort in Madrid.

The original goal of the PESA-CNIC-Santander study was to detect atherosclerosis long before the appearance of symptoms and thus to gain an understanding of the factors that trigger its development and progression.

After months of work with our partners at Amsterdam UMC and with Banco Santander’s medical services, we designed a lifestyle intervention for participants who are part of the PESA-CNIC-Santander cohort,” explained Dr. Inés García-Lunar, a cardiologist at the CNIC and first author of the study.

The intervention consisted of a program of 12 motivational sessions distributed over 3 years in which an expert psychologist provided participants with the tools to introduce heart-healthy changes into their lifestyle. Participants also were given a physical activity bracelet to monitor the number of steps per day and a sit-stand desktop that allowed them to alternate sitting and standing during working hours, thus reducing sedentary time.

More than 1000 PESA-CNIC-Santander study participants at Banco Santander were randomly assigned to follow the intervention during their working hours or to continue with their normal routines,” said Borja Ibáñez, CNIC Scientific Director and a cardiologist at Fundación Jiménez Díaz University Hospital.

“We found that individuals assigned to the intervention increased their level of physical activity, improved their diet, and reduced their sedentary time. And as a consequence of these behavioral changes, these participants’ blood pressure and cholesterol also decreased,” explained Dr. José María Castellano, a cardiologist at the CNIC and Scientific Director of the HM Hospitales Research Foundation.

“A very important result is that the effect of the intervention decreases over time, which suggests that programs of this type need even more frequent reinforcement to achieve sustained changes,” noted Dr. Ines Garcia-Lunar.

“The study represents a major finding, due to the complexity of implementing a program of these characteristics in a work environment, and this has been possible thanks to the hard work and commitment of all those involved, including the willing engagement of the participants,” explained Dr. Valentín Fuster, who is the principal investigator on the study.

Dr. Fuster has dedicated his professional career to cardiovascular research at the highest level and has led innumerable studies throughout the world aimed at promoting cardiovascular health at different stages of life, from childhood to adulthood. He concluded that “the results of this study send an optimistic message: A change to a more heart-healthy lifestyle is possible, even in adulthood, but needs subsequent reinterventions.”

TANSNIP-PESA is funded by Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) Carlos III through an Investigator-initiated Study grant to Icahn School of Medicine from AstraZeneca. The PESA study is cofunded by the CNIC and Banco Santander. The study also received funding from the Carlos III Institute of Health and the European Regional Development Fund.

"CNIC is like an oasis for science in Spain"

Dr Amelia Escolano was destined to be a scientist. Both of her parents were chemists, and research seemed to form part of her DNA. After completing her degree in biochemistry at the Universities of Oviedo and Turku (Finland), followed by a masters at the Centro de Biología Molecular Severo Ochoa in Madrid, she arrived at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), where she obtained her PhD in biochemistry and molecular biology. After a placement at the Rockefeller University of New York to complete her post-doctoral training, she now leads her own research group in Philadelphia (USA), where she is assistant professor at the Vaccine and Immunotherapy Center of the Wistar Institute. With the goal of producing a universal vaccine against HIV, Escolano’s group is working on a novel vaccination strategy called sequential vaccination, which consists of injecting a series of different versions of a viral component, in this case the HIV envelope protein, to induce an immune response giving broad protection against the AIDS virus. She also believes that SARS-CoV-2 and other viruses with the capacity to mutate can also be targeted with sequential immunisation

Where does your interest in researching vaccines stem from?





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During my pre-doctoral placement at CNIC, I studied the anti-inflammatory role of macrophages. But, on starting my postdoctorate in Dr Michel Nussenzweig’s laboratory at the Rockefeller University in New York, I took a radically different route. Dr Nussenzweig’s laboratory is internationally renowned for its research into HIV and B-cell biology, the cells that produce antibodies. That is where I began to work on the design of a universal vaccine to prevent infection by HIV, the virus that causes AIDS.

Now, I lead my independent laboratory at Philadelphia’s Wistar Institute, where my research into vaccination continues. My group is working on the design of new vaccination strategies against HIV and on analysing the immune response induced by our vaccination regimes, in particular the response to B and T cells.

So, how important has the knowledge acquired from COVID vaccines been for application to other diseases?

In fact, the opposite is true: all of the efforts that the research community has made to understand HIV or the flu virus over the years are what has facilitated the development of a vaccine for SARS-CoV-2 so quickly. The same techniques, the same methods, the same studies have been used and applied to analyse infection from SARS-CoV-2 and to design treatments and vaccines.

Many researchers who were working on HIV, influenza, and so on, threw themselves into studying SARS-CoV-2, and have used all of their  methodologies to study cellular and antibody response after infection or vaccination. It’s been interesting to see how all of these efforts and prior research devoted to other viruses has facilitated and accelerated the design and production of a vaccine against SARS-CoV-2.

What’s more, the success of mRNA vaccines and their validation in millions of people have promoted them being considered for other viruses, including HIV. It will be interesting to see the results of these trials in the near future.

Why is there still no vaccine for HIV?

 HIV is very special. On the one hand, it is a virus that mutates very quickly, creating a wide diversity of different strains. This is the same problem we find with the flu virus, which is why we have to update the vaccine every year because the strain in circulation differs. We don’t have a universal vaccine for the flu. An effective vaccine against HIV would have to induce production of a specific type of antibody that can neutralise a large number or the majority of HIV strains. These antibodies, called neutralising antibodies, cover a wide spectrum and attach to specific parts of the HIV virus that are conserved in all of the circulating HIV strains. To design a vaccine that can generate this type of antibody, we use the envelope protein of HIV, which is the equivalent of SARS-CoV-2’s spike protein. When this protein is used as an immunogen, the antibodies that are produced generally attach to areas of the envelope protein that are variable and are not conserved between the different strains, so those proteins would not protect against wide viral diversity. This immunity could protect you against strain 1, but would not protect against strains 2, 3, 4, 5 … This is one of the great challenges when designing a vaccine for HIV: it’s very difficult to focus the antibody response to given areas of the envelope protein so that these antibodies can protect you against all of the existing strains.

There are currently many researchers working on how to modify this protein so that, for instance, certain areas (epitopes) are not immunogenic, or to make the epitopes of interest more immunogenic, which is very complicated.

How are you trying to solve this problem in your research?

What we are using is a type of vaccination called sequential vaccination. Unlike traditional vaccination systems, where the immunogen itself is administered several times, for instance, in the case of SARS-CoV-2, what we do is inject different versions of the immunogen, one after another, in order to target antibody response to the epitopes of interest and induce maturation of these antibodies so they acquire the capacity to neutralise HIV. We start by injecting a version of the HIV envelope that is highly modified and subsequently, instead of re-injecting the same one, we inoculate another that is a little less modified, more similar to the natural protein of the envelope. The envelope proteins are administered sequentially, with increasingly less modification until the final injection, which is the unmodified, natural type.

We are currently designing different sequential vaccination protocols that we are testing on different animal models including murine and simian ones.

Is it used for other diseases apart from HIV?

Sequential vaccination is being tested in the context of other viral infections like the flu or COVID. It is a type of vaccination that can be very useful to induce immunity against viruses that are highly variable. In that way, we could get antibodies with the capacity to neutralise a wide spectrum of flu, SARS-CoV-2 or HIV viruses. What’s more, sequential vaccination could be useful to induce immunity to bacteria and cancer, an area that we would like to explore in the near future.

Did your research at CNIC already focus on viruses?

At CNIC, I worked on macrophages and their anti-inflammatory role in different pathological contexts. What we saw was that in macrophages, when the phosphatase calcineurin is inhibited or deleted, they acquire an anti-inflammatory phenotype that contributes to reducing different models of inflammation in mice. My thesis research project was in the field of immunology, but not related with virus, vaccines or B-cells, which is what I am currently studying in my Philadelphia laboratory. The step to post-doctoral work was a radical change as regards the focus of my research.

How did that change come about?

Towards the end of my thesis at the CNIC, I decided to do a pre-doctoral placement abroad with the idea of exploring laboratories for my post-doctoral research. Thanks to the recommendation of Dr Almudena Ramiro, I decided to go to Dr Michel Nussenzweig’s laboratory at the Rockefeller University in New York, where I did a three-month placement. After those three months, I returned to CNIC, defended my thesis, published my article and afterwards returned to the Rockefeller to do my post-doctoral work. During the first months I worked with macrophages and dendritic cells, helping a colleague to complete their studies, but I soon gravitated towards HIV and the design of vaccination protocols. At the time I arrived in New York, this was a hot topic and a completely new area for me, with all of the attendant difficulties, but I could never have imagined a better place to make that transition. My post-doctoral period was extremely productive and enriching. Dr. Nussenzweig was a fabulous mentor, and I received the first-class training that meant I could become an independent researcher in the USA.

 What change did you notice between working at CNIC and in the United States?

The first difference I noticed when I arrived in the USA was that society in general values and gives recognition to scientists. Spain still does not understand that science and innovation are pillar stones of the economy and progress.

Rockefeller University is one of the top scientific institutions in the world. Its policy is to try to provide scientists with everything we need to do our job without having to worry too much about other things. And, judging on the amount of recognition it receives, it seems to work.

My experience at CNIC was fantastic. My mentor, Dr Dr. Juan Miguel Redondo, and my colleagues offered me everything I needed in my training as a scientist, and even today they  continue to support and help me all they can, for which I am profoundly grateful. I don’t think that my experience is representative of what doing a doctorate in Spain is like. I never felt that my work was limited by laboratory resources, but the CNIC is like an oasis for science in Spain. Colleagues of mine doing their theses in other Spanish institutions, and students that I have spoken to recently, have had to work on their thesis without receiving a salary. Their situation is precarious, and it is deplorable.

When you were studying at university or in CNIC, did you see going abroad as a necessary step?

From the very start of my degree, I knew that I would go abroad. In my case, it was not a forced decision. Going abroad is a way of developing, coming into contact with new stimuli and environments, meeting people and learning. Leaving Spain, or your comfort zone, is highly recommendable whenever possible. The last semester of my degree was spent in a laboratory at Turku University in Finland. That was my first experience abroad and it was one of the best of my life. It helped me gain a better understanding of myself, to know other cultures, other ways of seeing things, improve my English, and I had a great time. It was a very enriching experience. These experiences serve to put yourself to the test, discover your limits, and gain maturity and vision.

What were your professional decisions based on?

I now realise that when I finished my degree I did not have enough information to evaluate all of the options open to me, so my decisions were somewhat limited by a lack of information. My first decision was to stay in Oviedo and do the thesis. However, before starting the thesis, and almost unexpectedly, I received a grant from the Spanish National Research Council, the CSIC, for an introduction to research in Madrid. This period of time in Madrid made me rethink and reconsider my options. I changed my mind and decided to start my thesis in that laboratory in Madrid and a few months later I was recruited to Cincinnati. After a time in Cincinnati, I realised that it was not what I wanted and I returned to Spain to start a new thesis at CNIC, in Dr Redondo’s laboratory, where I received an extraordinary training. When I made that decision, I did not even consider the option of saying in the USA, which could have been better or worse. Nowadays there is more information. It is important that students devote time to studying their own options and learning from the mistakes and successes of others so they can make informed decisions. The end of a degree and a thesis are stressful moments when we are expected to make decisions that can mark our future careers. In my case, it was not until the post-doctorate that I felt mature and informed enough to make my next decision, which was to establish myself as an independent researcher at the Wistar Institute in Philadelphia.





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Did your predoctoral and post-doctoral experiences help when it came to forming your own group?

Both my thesis and my post doctorate were very long, six to seven years each, so I had time to mature and the training necessary to tackle the new stage.  During my thesis I learned to design experiments, to analyse them and, to conclude, I learned a multitude of techniques, to work in a team, to present my work in public…My post-doc was also very complete and highly productive. It allowed me to specialise and gain a foothold in my area of research. When I finished my post-doc, and even before that, I felt that I was ready for independence. It has been a long journey, but each and every complication I have had to face in my career has helped me to become resilient, which is an indispensable quality in science.

What is your experience of being a woman in science?

The world of science, like many others, is still dominated by men, and the lack of female presence in some contexts is surprising. Little by little, women are carving out a niche in positions of greater responsibility, and conditions are becoming more equal. From my position, I would encourage all women not to let themselves be intimidated and to pursue their goals without fear. During my career I have worked with some extraordinary women, who have incredible strength, women who forged the path for those of us who have come later. I hope that my career also serves to forge a path for new generations of women in science.

You are now the mentor of the researchers in your group. How important is mentoring?

The role of mentor is indispensable, and one that we have to prepare for mainly during the post-doc. It is not a trivial thing; each student is different and needs to be treated differently. You have to know whether to give the help or independence that each person needs to develop in the most efficient way. You need to know how to give recognition and thanks, but also how to call things to order when necessary. My hope and aim are that all of the people who work with me enjoy their jobs. I have enjoyed myself enormously doing what I do, and I hope to be able to transmit my enthusiasm for science to my students. I also trust that my experience serves them when it comes to making their decisions.

Dr. Amelia Escolano participated in the Sequential vaccination to induce somatic hypermutation Seminar: From naïve PhD student to group leader

eLife: CNIC scientists uncover opposing roles of p38 proteins in cardiac hypertrophy

A study carried out by scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and led by  Dr. Guadalupe Sabio has identified a key role for the MKK3/6–p38γ/δ signaling pathway in the development of cardiac hypertrophy. The results, published in the journal eLife, suggest that inhibition of p38γ/δ could be a useful therapeutic strategy for diseases such as hypertrophic cardiomyopathy; however, this avenue remains unexplored because of the lack of specific inhibitors for these kinase enzymes. The study also shows the opposite effect upon inhibition of another member of this protein family, p38α, indicating that long-term clinical use of p38α inhibitors to treat chronic disease risks damage to the heart.


The human heart beats approximately 100,000 times a day to pump blood throughout the body, supplying the oxygen and nutrients that the body’s organs need to function. The heart has to satisfy this demand for blood not only under normal conditions, but also under conditions of stress. To achieve this, the heart has the capacity to increase in size, a process called hypertrophy. Cardiac hypertrophy is how the heart grows after birth and is also a normal response to physical exercise, explained first author Rafael Romero. But cardiac hypertrophy can also be triggered by high blood pressure and some genetic diseases.

The contractile cells of the heart, called cardiomyocytes, contain numerous molecular pathways whose activation promotes cardiac hypertrophy. “One of these is the p38 pathway, which is activated in response to stress stimuli,” explained Romero. The p38 proteins control a broad spectrum of processes, and their dysregulation has been linked to numerous diseases, making them promising pharmacological targets for clinical use. Nevertheless, specific inhibitors have been identified for only one of the p38 isoforms, p38α. As Dr. Sabio recognized, “the results of clinical trials to date have been disappointing, but other proteins of the pathway, such as p38γ, p38δ, or the upstream activator MKK6, are interesting possible alternative pharmacological targets”.

With this in mind, the team investigated the safety and potential long-term negative effects of inhibiting MKK6. Using mice genetically engineered to lack MKK6, the scientists showed that the absence of this protein reduced life expectancy. These mice developed cardiac hypertrophy when young and developed cardiac dysfunction as they got older. Using other mouse models, the researchers found that when MKK6 is absent the activation of p38α

is significantly reduced.Nevertheless, inactivation of p38α promoted an unexpected activation of the other branch of the pathway, consisting of the proteins MKK3, p38γ, and p38δ. This activation induced another of the key pathways in the development of cardiac hypertrophy, the mTOR pathway.

“We have identified a key role for the MKK3/6–p38γ/δ pathway in the development of cardiac hypertrophy,” said Dr. Sabio. “This has implications for the use of p38α inhibitors to treat chronic conditions, since they could be cardiotoxic over the long term. At the same time, our results indicate that efforts should be focused on the search for specific inhibitors of p38g and p38δ that could be used to treat cardiac disease.”

The study recieved support from the following bodies: MINECO-FEDER, American Heart Association; EFSD/Lilly European Diabetes Research; Fundación AECC y Comunidad de Madrid IMMUNOTHERCAN-CM; Instituto Nacional de Corazón, Pulmón y Sangre; Fundación “la Caixa”; Fundación La Marató TV3: Programa FP7 Marie Curie; EFSD Rising Star y JDC-2018-Incorporación (MIN/JDC1802).

Cell Stem Cell: Researchers at CNIC, UPF, ICREA, CIBERNED and CIBERFES identify a mechanism that maintains mitochondria function in muscle stem cells and that can be stimulated in old age

Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Universidad Pompeu Fabra, ICREA, Centro de Investigación Biomédica de Enfermedades Neurodegenerativas (CIBERNED) and Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES) have identified a physiological mechanism that sustains the regenerative capacity of muscle stem cells, and that fails at old age. This failure can be overcome genetically and pharmacologically, hence restoring old stem cell regenerative functions.



Skeletal muscle regeneration depends on a muscle stem cell population (satellite cells) in a dormant or quiescent state, a situation that can be triggered by damage or stress to form new muscle fibres and expand in new stem cells.



The regenerative functions of these stem cells are known to decline with ageing. Dr. Pura Muñoz-Cánoves, senior investigator at the National Centre for Cardiovascular Research (CNIC) in Madrid, and ICREA professor at the MELIS Department at Pompeu Fabra University (UPF) in Barcelona, and Ciberned, and Dr. José Antonio Enríquez, senior investigator at CNIC and CIBERFES, and their colleagues, have found in experiments with mice that mitochondrial dynamics are required for tissue regeneration. Mitochondrial fission facilitates muscle stem cell function via OXPHOS and mitochondrial autophagy (mitophagy) regulation.



Xiaotong Hong, the PhD student that has conducted the study, together with her colleagues, has shown that genetic loss of the mitochondria fission regulator DRP1 in muscle stem cells (or during aging) blunts their proliferation and regenerative capacity, whereas its reestablishment rescues these defects.


According to the results presented in Cell Stem Cell, normalizing mitochondrial dynamics (or increasing OXPHOS and mitophagy) in aged muscle stem cells restores tissue regeneration. This opens the way to improve the health of elderly people who are debilitated by the loss of muscle regenerative capacity.

This scientific study has also involved the collaboration of researchers at the University of Cordoba and the University of Padua (Italy). The study was funded in part by grants from the European Research Council (ERC), the Spanish Ministry of Science and Innovation, La Caixa-Health, Human Frontier Science Program and Leduq Foundation (LeduqRedox).

Mitochondrial dynamics maintains stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. Xiaotong Hong et al (2022). Cell Stem Cell, 2022

NEJM: The polypill reduces cardiovascular mortality by 33% in patients treated after myocardial infarction

The polypill developed by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Ferrer, which includes three drugs (aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin), is effective at preventing secondary adverse cardiovascular events in people who have previously had a heart attack. The polypill reduces mortality from cardiovascular causes in this population by 33%.

This is the finding of the SECURE study, coordinated by CNIC. The study results were presented today in a Hot Line session at the European Society of Cardiology meeting (ESC 2022) in Barcelona and are published in The New England Journal of Medicine (NEJM).

Dr. Valentín Fuster, principal investigator of the SECURE study, CNIC General Director, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, said “the results of the SECURE study show for the first time that the polypill, which contains aspirin, Ramipril, and atorvastatin, achieves clinically relevant reductions in the recurrent cardiovascular events among people who have recovered from a previous heart attack.”

SECURE included 2499 patients from 7 European countries (Spain, Italy, Germany, the Czech Republic, France, Poland, and Hungary) recovering after a myocardial infarction. The study participants were randomly assigned to receive standard therapy or the CNIC polypill. The average age of the participants was 76 years, and 31% were women. The study population included 77.9% with hypertension, 57.4% with diabetes, and 51.3% with a history of tobacco smoking.

The SECURE trial analyzed the incidence of four major cardiovascular events: death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, and emergency coronary revascularization (the restoration of blood flow through a blocked coronary artery). The study followed patients for an average of 3 years and produced conclusive results: patients taking the polypill had a 24% lower risk of these four events than patients taking the three drugs separately.

The standout finding of the study is the effect of the polypill on the key outcome of cardiovascular related death, which showed a relative reduction of 33%, from 71 patients in the group receiving standard treatment to just 48 in the polypill group.

The study also found that patients in the polypill group had a higher level of treatment adherence than those in the control group, thus confirming the findings of the earlier FOCUS2 study, also funded by the European Union.

 “Adherence to treatment after an acute myocardial infarction is essential for effective secondary prevention.  The polypill, being a very simple strategy that combines three essential treatments for this type of patient, has proved its worth because the improved adherence means that these patients are receiving better treatment and therefore have a lower risk of recurrent cardiovascular events. said Dr. José María Castellano, study first author and Scientific Director of Fundación de Investigación HM Hospitales.

According to Oscar Pérez, Chief Marketing, Market Access and Business Development Officer at Ferrer, “the 33% reduction in cardiovascular mortality demonstrates the efficacy of treatment with Trinomia3 compared to standard treatment. These results ratify our purpose of making a positive impact in society and represent an important step in our mission to provide significant and differential value to people who suffer from serious health conditions”.

Concluding, Dr. Fuster said “the SECURE study findings suggest that the polypill could become an integral element of strategies to prevent recurrent cardiovascular events in patients who have had a heart attack. By simplifying treatment and improving adherence, this approach has the potential to reduce the risk of recurrent cardiovascular disease and death on a global scale.”

The SECURE trial was funded by the European Union Horizon 2020 research and innovation program (trial identifier NCT02596126).


Polypill Strategy in Secondary Cardiovascular Prevention Castellano JM, Fuster V et al. New England Journal of Medicine (NEJM). 2022 Aug.Castellano JM, Sanz G, Peñalvo JL, Bansilal S, Fernández-Ortiz A, Alvarez L et al.  A polypill strategy to improve adherence: results from the FOCUS project. J Am Coll Cardiol. 2014 Nov 18-25;64(20):2071-82Ficha ténica Trinomia®: FICHA TECNICA TRINOMIA 100 MG/40 MG/10 MG CAPSULAS DURAS (

* Trinomia®, Sincronium®, Iltria®. Contiene Ácido acetilsalicílico 100mg, Atorvastatina 20/40mg y Ramipril 2,5/5/10mg.

Polypill Strategy in Secondary Cardiovascular Prevention. NEJM 2022: Jose M. Castellano, Stuart J. Pocock, Valenti Fuster… et all for SECURE investigators. 10.1056/NEJMoa2208275

Insufficient sleep in teenagers is associated with overweight and obesity

Adolescents who sleep less than eight hours a night are more likely to be overweight or obese compared to their peers with sufficient sleep, according to research presented at ESC Congress 2022.

Shorter sleepers were also more likely to have a combination of other unhealthy characteristics including excess fat around the middle, elevated blood pressure, and abnormal blood lipid and glucose levels.

“Our study shows that most teenagers do not get enough sleep and this is connected with excess weight and characteristics that promote weight gain, potentially setting them up for future problems,” said study author Mr. Jesús Martínez Gómez, a researcher in training at the Cardiovascular Health and Imaging Laboratory, Spanish National Centre for Cardiovascular Research (CNIC), Madrid, Spain. “We are currently investigating whether poor sleep habits are related to excessive screen time, which could explain why older adolescents get even less sleep than younger ones.”

This study examined the association between sleep duration and health in 1,229 adolescents in the SI! Program for Secondary Schools trial in Spain, a collaborative research effort by the SHE-“la Caixa” Foundation, the University of Barcelona and CNIC. Participants had an average age of 12 years at baseline with equal numbers of boys and girls.

Sleep was measured for seven days with a wearable activity tracker three times in each participant at ages 12, 14 and 16 years. For optimal health, the American Academy of Sleep Medicine advises sleeping 9 to 12 hours a night for 6 to 12 year-olds and 8 to 10 hours for 13 to 18 year-olds.To simplify the analysis, the study used 8 hours or more as optimal. Participants were categorised as very short sleepers (less than 7 hours), short sleepers (7 to 8 hours), and optimal (8 hours or more).

Overweight and obesity were determined according to body mass index. The researchers calculated a continuous metabolic syndrome score ranging from negative (healthier) to positive (unhealthier) values that included waist circumference, blood pressure, and blood glucose and lipid levels.

At 12 years of age, only 34% of participants slept at least 8 hours a night, and this dropped to 23% and 19% at 14 and 16 years of age, respectively. Boys tended to get less sleep. Teenagers who got the most sleep also had better quality sleep, meaning they woke up less during the night and spent a higher proportion of the time in bed sleeping compared to those with shorter sleep. The prevalence of overweight/obesity was 27%, 24% and 21% at 12, 14 and 16 years of age, respectively.

Associations between sleep duration, overweight/obesity and metabolic syndrome score were analysed after adjusting for parental education, migrant status, moderate-to-vigorous physical activity, smoking status, energy intake, city (Madrid or Barcelona) and school.

The connections between insufficient sleep and adverse health were independent of energy intake and physical activity levels, indicating that sleep itself is important

Compared with optimal sleepers, overweight/obesity was 21% and 72% more likely in very short sleepers at 12 and 14 years, respectively. Short sleepers were 19% and 29% more likely to be overweight/obese compared with optimal sleepers at 12 and 14 years, respectively. Similarly, both very short and short sleepers had higher average metabolic syndrome scores at 12 and 14 years compared with optimal sleepers.

Dr Rodrigo Fernandez-Jiménez, group leader of the Cardiovascular Health and Imaging lab, said: “The connections between insufficient sleep and adverse health were independent of energy intake and physical activity levels, indicating that sleep itself is important. Excess weight and metabolic syndrome are ultimately associated with cardiovascular diseases, suggesting that health promotion programmes in schools should teach good sleep habits. Parents can set a good example by having a consistent bedtime and limiting screen time in the evening. Public policies are also needed to tackle this global health problem.”

JACC: CNIC scientists describe key features of one of the most frequent forms of hereditary dilated cardiomyopathy

A study conducted at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Hospital Universitario Puerta de Hierro de Majadahonda in Madrid describes key features of one of the most frequent forms of genetic dilated cardiomyopathy, caused by mutations in the myosin heavy chain gene (MYH7).

Understanding the specific characteristics of the different genetic subtypes of dilated cardiomyopathy is the first step towards personalized treatment of patients with this disease, says study leader Dr. Pablo García-Pavíaa, cardiologist at Hospital Puerta de Hierro and a researcher at the CNIC and in the CIBER de Enfermedades Cardiovasculares (CIBERCV).

Dilated cardiomyopathy is the most frequent cause of heart failure in young people and the principal indication for heart transplantation in the world. The disease is characterized by an enlargement of the heart accompanied by a decrease in its ability to pump blood. Dilated cardiomyopathy often features arrhythmias, and patients have an elevated risk of sudden cardiac death.

Hereditary forms of cardiomyopathy are caused by errors in the DNA genetic code and can affect multiple members of the same family. Hereditary genetic mutations are responsible for approximately half of all cases of the disease.

Dilated cardiomyopathy is the most frequent cause of heart failure in young people and the principal indication for heart transplantation in the world

The identification of the cause of a patient’s dilated cardiomyopathy in a genetic mutation allows for a more precise treatment strategy and the screening of relatives to determine if they have also inherited the mutated gene and require medical monitoring.

The study collected data from 147 patients and family members with mutations in the MYH7 gene. The study included contributions from 40 centers in 10 countries, making this the most ambitious study addressing this disease to date.

This collaborative effort has revealed particular characteristics of MYH7-related dilated cardiomyopathy.

One of these characteristics is that a high proportion of patients with MYH7 mutations (16%) develop the disease in infancy, whereas other forms of the disease almost always appear later in life (between the ages of 40 and 50 years). “This finding establishes the wisdom of monitoring the children of patients with this form of dilated cardiomyopathy from infancy,” indicated Dr. García-Pavía.

Another key finding is that patients with MYH7 gene mutations have a weaker response to drug treatment than those with other genetic forms of dilated cardiomyopathy. Despite this, sudden cardiac death, the most feared complication of dilated cardiomyopathy, is less common in MYH7-related dilated cardiomyopathy than in other forms of the disease and only affects advanced forms of the disease.

Dr. Fernando de Frutos, cardiologist at Hospital Puerta de Hierro and first author on the study, explained that “collaborative projects of this type are essential for understanding the mechanisms by which the gene mutations cause heart failure and pointing the way towards personalized treatments for patients and family members.”

Specific treatments for MYH7-related dilated cardiomyopathy are currently under investigation, and these treatments could represent a turning point for the management of these patients.

Fernando de Frutos, Juan Pablo Ochoa…, Pablo Garcia-Pavia, and for the European Genetic Cardiomyopathies Initiative. Natural History of MYH7-related Dilated Cardiomyopathy. J Am Coll Cardiol, 2022. Epublished DOI: 10.1016/j.jacc.2022.07.023

JACC: Scientists at the CNIC and Hospital Puerta de Hierro develop a tool to determine if dilated cardiomyopathy has a genetic origin

Scientists at the CNIC and Hospital Universitario Puerta de Hierro Majadahonda have developed a software application that predicts the likelihood that a case of dilated cardiomyopathy is caused by a genetic mutation. The research was carried out in collaboration with hospitals in Spain, Italy, and the Netherlands. The findings, published in the Journal of the American College of Cardiology (JACC), will allow physicians to adjust the treatment of dilated cardiomyopathy patients appropriately and to identify family members who have also inherited the disease. The software application is available online at .

Dilated cardiomyopathy is the most frequent cause of heart failure in young people and the main indication for heart transplantation in the world. The disease is characterized by enlargement of the heart accompanied by a decine in its capacity to pump blood, and patients with this condition are at high risk of arrhythmias and sudden cardiac death.

In approximately 30% of patients with dilated cardiomyopathy, the disease arises as a consequence of a heritable genetic mutation. Knowing that a patient’s disease has a genetic cause allows physicians to adjust treatment appropriately and to identify other family members who have also inherited the disease.

Nevertheless, in many places in the world dilated cardiomyopathy patients do not undergo routine genetic screening due to the considerable cost of this procedure, which gives a positive result in only 1 in every 3 patients.

Cardiomyopathy is the most frequent cause of heart failure in young people and the main indication for heart transplantation in the world

The new study was led by cardiologist Dr. Pablo García-Pavía of Hospital Puerta de Hierro, and who is also a research scientist at the CNIC and in the Spanish cardiovascular research network (CIBERCV). The study analyzed the clinical characteristics, electrocardiograms, and echocardiography data of a group of 1015 dilated cardiomyopathy patients who underwent genetic screening at 20 Spanish hospitals.

The results identified 5 parameters that were more frequent in patients in whom the disease was caused by a genetic mutation.

The combined scoring of these 5 parameters in a software application, called the Madrid Genotype Score, allows the classification of patients according to the likelihood that their disease has an origin in a heritable genetic mutation. First author Dr. Luis Escobar explained that “among patients positive for most of these parameters, the disease was more likely to have a genetic cause, whereas among patients negative for the parameters or postive for only one or two, the probability was lower. A genetic cause was found in only 2% of patients negative for all 5 parameters.”

The researcher team verified the predictive ability of the tool in an independent group of 1097 dilated cardiomyopathy patients from Italy and the Netherlands.

The software application has been made feely available to medical professionals via the website, and the tool is expected to facilitate the genetic screening of dilated cardiomyopathy patients, given that it identifies those patients most likely to have a causal genetic mutation.

Escobar-Lopez L; Ochoa JP; Royuela A…Garcia-Pavia P., et al. Clinical Risk Score to Predict Pathogenic Genotypes in Patients with Dilated Cardiomyopathy. J Am Coll Cardiol 2022;80:1115–1126

Viable cyanobacteria in the deep underground of Rio Tinto

  • A study led by the Centro de Astrobiología (CAB, CSIC-INTA) has detected for the first time the presence of viable cyanobacteria in the deep subsurface (below 600 meters of depth)
  • The finding took place at the rocky massif sulphide ore of the Iberian Pyrite Belt (IPB; at Río Tinto, Huelva), an area in the South of Spain considered in astrobiology as a terrestrial analogue of early and wet Mars.
  • The found cyanobacteria apparently use as an energy source a mechanism that at the Earth surface protects them from the light.


Cyanobacteria are very versatile photosynthetic organisms that live in the majority of ecosystems, from sea systems to extremely arid deserts. Until now, their ecological range seemed to be restricted to environments with at least occasional occurrence of sunlight. A study led by researchers of the Centro de Astrobiología (CAB) and published by the journal Proceedings of the National Academy of Sciences (PNAS), has detected the presence of viable cyanobacteria in samples of deep rocky cores of the Iberian Pyrite Belt (area in which Rio Tinto originates, in the Huelva province of Spain).

In the study, done in the framework of the projects Advanced Grant of the European Research Council (ERC) and the Spanish RETOS-MINECO, molecular, microscopic, and metagenomic evidence is presented of the preponderance of cyanobacteria in some niches of the deep underground of IPB. The analysed core samples were obtained from two purposed designed deep drillings , within the ERC’s IPBSL project (Iberian Pyrite Belt Subsurface Life). This project, undertaken by CAB between the years 2010 and 2015, had as the main objective to characterize the geomicrobiology and operating metabolisms in the deep ecosystems of the IPB.

During the drillings, the core samples extracted were analysed with the SOLID-LDchip system, a biochip used to detect signs of life that is under development at CAB for planetary exploration. Researchers detected from the first moment and on site some immunologic clues of the presence of cyanobacteria. The initial result of the analysis confirmed later by means of other techniques, such as the sequencing of the ribosomal 16S gene extracted from the analysed rocks, or the visualization of cyanobacteria with microscopy and the use of specific fluorescent probes capable of binding to them. Later on, the sequence of two metagenomes (collective pool of genes from an environmental sample) at different depths, 420 and 607 m, respectively, allowed researchers to fully confirm the presence of cyanobacteria.

As energy source, the found cyanobacteria seem to use a natural “security valve” that at the Earth surface protects them from the light. The system redirects excess energy towards the outside of the cell, transferring electrons towards substances such as oxidised metals or organic matter. Paradoxically, the same system would become activated in conditions of darkness and anoxia present in the deep underground, allowing them to obtain energy despite the absence of light.

The results of the study suggest that cyanobacteria can play a very relevant role as primary producers in the deep biosphere of the Earth. Also, this ecological niche, until recently unknown, highlights the versatility of cyanobacteria, one of the most ancient groups of microorganisms on Earth. It as well allows to propose new models on their origin and evolution, and to suggest the possible presence of similar organisms in current or primitive biospheres in other planets and their moons.


Image credits:

All images were kindly provided by the Centro de Astrobiología.