Myocardial infarction is the leading cause of death in developed countries and the third leading cause of death in developing countries. Seven out of 10 people survive a heart attack, but the heart has little regenerative capacity. Nor do current therapies prove to be effective, which ultimately leads to associated health costs.
To a large extent, the poor regenerative capacity of this tissue has to do with a very limited activity of the vascular cells in the infarcted area. This causes insufficient blood to reach that area and limits the ability to heal and regenerate. “Our project tries to characterize and identify genetic pathways and pharmacological compounds that can activate vascular cells in infarcted areas, so as to effectively promote their growth and stimulate the regenerative capacity of the tissue, which could open the door to discover new strategies for prevent heart failure», explains Rui Benedito, a researcher at the Cardiovascular Research Center (CNIC), whose work is supported by ‘la Caixa’.
Will the heart be able to regenerate after a heart attack in the future?
-Some of the basic science studies suggest that one day it will be possible to induce some kind of regeneration or repair of the heart. The heart is made up of many different types of cells, and some are easier to reprogram and regenerate than others.
-What are the main obstacles for you to regenerate?
-After a heart attack, many cardiomyocytes (heart muscle cells) are lost in the injured area and this leads to loss of the heart’s pumping function. Surviving cardiomyocytes are inactive and have a very limited ability to proliferate or regenerate. Some recent research suggests that it may be possible to pharmacologically reprogram these cells and grow some of them, but so far this also leads to loss of their contractile function. Other studies have focused on the regeneration and growth of other cardiac cell types that are also essential for heart health and function, such as vascular cells. Our group knows how to activate and induce the proliferation and mobilization of vascular cells.
-What characteristics do these vascular cells have?
-After a heart attack there is a significant loss not only of muscle cells, but also of endothelial cells, the cells that form the capillaries of the heart. This leads to loss of blood flow to the heart muscle and subsequent loss of heart function. We now know that the endothelial cells that make up the arteries are more resistant to heart attack than the capillary cells. However, these surplus arterial cells are much less proliferative. Furthermore, injured heart muscle does not provide the necessary cocktail of factors for it to grow and mobilize properly so that it can effectively make new blood vessels.
-Your project financed by la Caixa seeks to understand and promote the growth and regenerative functions of blood vessels in heart diseases. What are you going to investigate?
-In the last 10 years our laboratory has been studying how to efficiently induce the proliferation and mobilization of vascular cells to form new blood vessels, a process called angiogenesis. We will now use this knowledge to investigate and test different drug and gene therapies to effectively induce angiogenesis in infarcted hearts.
-While the skin and other body tissues retain the ability to repair themselves after injury, the same is not true of the heart. What can be learned from these cells?
-We know that these same cells, when they are in an embryo or in early stages of life, have the ability to proliferate. And they lose it once the heart matures. There are many groups, including at the CNIC, investigating how to make heart muscle cells proliferate again as in embryos. Our approach is different, we want to learn how to grow blood vessels and provide the factors that muscle cells need to grow or make them more functional.