Dr. Sergio Lavandero: “Challenges and opportunities in cardiovascular research”

The Advanced Center for Chronic Diseases, ACCDiS (www.accdis.cl), has developed Research of Excellence that has allowed to position itself as a regional and national science reference, in terms of basic, clinical and applied studies linked to the development of prevalent and chronic pathologies in Chile. In this context, this FONDAP Center auspices multiple collaborative teams working in laboratories headed by outstanding scientists.

One of the laboratories is led by Dr. Sergio Lavandero (Director and Principal Investigator of ACCDiS), who together with his team, investigates the development of cardiovascular diseases in Chilean population, which also represent much of the mortality in our country and the world.

Dr. Sergio Lavandero is a prominent Chilean scientist, recognized for its high-quality research and production efficiency. This is summarized in 227 publications to his credit, being cited more than 13.139 times according to Google Scholar, considered very important in any field of science.

Currently, he is Full Professor of the Faculty of Chemical and Pharmaceutical Sciences, and the Faculty of Medicine of the University of Chile. He is also Adjunct Professor in the Division of Cardiology, University of Texas Southwestern Medical Center (Dallas, Texas). During his career, Dr. Lavandero was Chairman and member of the Upper Council of Science of FONDECYT, President of the Chilean Society of Biochemistry and Molecular Biology, Member of the Evaluation Council and Vice-Rector of Research at the University of Chile. Prof. Lavandero is also a member of the Chilean Academy of Sciences and member of the Academy of Pharmaceutical Sciences of Chile.

Dr. Lavandero is Associate Editor of the prestigious “Circulation” journal (http:circ.ahajournals.org/) and integrates the Editorial Boards of the journals “American Journal of Physiology-Endocrinology & Metabolism”, “Cell Death & Diseases” and “BBA Molecular Basis of Diseases”. He is also ad hoc reviewer from prestigious international journals and national and international agencies that support scientific research.

What are cardiovascular diseases?

They are those that affect the circulatory system, made by the heart, arteries, veins, and capillaries.

Several diseases affect your performance, which includes: high blood pressure, myocardial infarction, encephalic vascular accidents, Angina pectoris, arrhythmias, heart failure and sudden death, among others. These diseases are incurable, slow progression, high cost and represent nearly 30% of the total mortality. They are classified as non-communicable chronic diseases, and together with cancer, diabetes mellitus and respiratory diseases account for 84% of the mortality in our country. The prevalence of certain cardiovascular diseases is high, especially hypertension.

According to the latest National Health Survey (ENS) 2010, 30 of every 100 Chileans adults suffer from arterial hypertension. In addition, its prevalence increases significantly as we age and if it is not controlled in time, its consequences are devastating, particularly on the kidney, heart & brain. On the other hand, ischaemic heart disease caused by partial occlusion (Angina pectoris) or complete (myocardial infarction), also generate damage to the myocardium of the coronary arteries, due to the progressive and silent accumulation of cholesterol and/or thrombus formation of platelets on the surface of the atherosclerotic plaque.

Both hypertension and ischaemic heart disease are the two main disorders that lead to the development of heart failure.

How does the heart work?

The heart is a contractile bomb that transforms the chemical energy contained in nutrients (glucose and fatty acids) into mechanical work. This organ mobilizes around 7,600 liters of blood per day.

The heart is divided into two atria and two ventricles. These cameras work harmoniously and coordinated, experiencing cycles of muscle contraction and relaxation. Its walls consist of cardiomyocytes, cells that work tirelessly and automatically all day and night from the beginning until the end of our existence. These cells represent only 33% of the total number of cells of the heart, but they contain the basic contractile units called sarcomeres.

The notable specialization of cardiomyocytes throughout evolution had a high price because they cease to divide a few weeks after birth, being almost fixed number nearly for the rest of our life. However, these cells can die by various mechanisms produced by chronic stress observed in the patients with hypertension without treatment or in individuals who suffer a myocardial infarction, in which many cardiomyocytes die acutely product from the lack of blood (ischemia) and subsequent reperfusion.

Heart failure is a syndrome because it is the final clinical manifestation of most of the other cardiac pathologies and is characterized by the progressive death of cardiomyocytes and the concomitant decline of contractile function of this organ essential for life.

Our lab works to understand its structure, the intracellular communication network, and function under normal and pathological conditions, as well as their energy metabolism. His incessant mechanical work demands large amounts of energy in the form of ATP. Cardiomyocytes generate nearly 6 kg of ATP a day in a normal individual, which is used immediately after generation so we do not experience any change in our body weight.

Role of mitochondria in cardiomyocytes

The high demands of the energy of cardiomyocytes are by provided the mitochondria. These subcellular organelles were originally characterized as elongated double membrane cylinders. This description changed to a mitochondrial network undergoing dynamic changes in their morphology in the same cell, being able to appreciate isolated mitochondria (similar to a pea) and other elongated ones (spaghetti-like). This last phenotype is associated with a state of increased power generation by mitochondria.

One of our main findings in recent years was to discover that insulin, an energy metabolism regulator hormone, stimulates the fission and mitochondrial function in the cardiomyocyte (Parra et al., Diabetes 2014). However, it was striking to find that mitochondria are also active in the death of a cardiomyocyte, as a significant reduction in the potential of the mitochondrial membrane releases molecules that are associated to death by apoptosis (intrinsic pathway) of the cardiomyocyte.

In general, our research group aims to understand the molecular mechanisms responsible for the normal functioning of the heart and identify basic alterations that explain the genesis and development of major cardiovascular diseases. This new knowledge will help into prevention, cure, and treatment of these diseases.

Cardioprotective

We have also investigated various molecules that regulate the functioning of the heart: One of them is a peptide known as angiotensin-(1-9), discovered through a collaborative work with researchers of the Pontifical Catholic University of Chile (PUC): DRS. María Paz Ocaranza and Jorge Jalil.

Our investigations have shown that this peptide is cardioprotective that prevents or attenuates the cardiomyocyte death. Together with the team of Dr. Marcelo Kogan, we are investigating how this peptide works to develop new nanobiotechnological forms of administration.

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Journalist: Patricio Grunert Alarcón. ®
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