Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.
The findings, published in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.
The heart has long been considered to be an organ without regenerative potential. Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.
The researchers postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.
Using sophisticated technologies to track cells in a mouse model the team demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries, a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.
The finding that coronary arteries house a cardiac stem cell ‘niche’ has interesting implications. Coronary artery disease, the No. 1 killer in the United States, would impact this niche. The study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated.
The current research follows a previous study in which the team demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue. It looks like the same endothelial system generates myocytes (muscle cells) during homeostasis and then switches to generate scar tissue after a myocardial infarction. After injury, regeneration turns to fibrosis.
Understanding this switch could lead to new strategies for restoring regeneration and producing new heart muscle after a heart attack, during aging or in disease conditions such as diabetes and high blood pressure.
The researchers summise that if they can understand the molecular mechanisms that regulate the fate switch that happens after injury, perhaps they can use some sort of chemical or drug to restore regeneration and make muscle instead of scar. The team state that there is an opportunity here to improve treatment for people who come into the clinic after myocardial infarction.
Source: Vanderbilt University