Researchers at Vanderbilt University report that endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue. They believe their study (“Endothelial Cells Contribute to Generation of Adult Ventricular Myocytes during Cardiac Homeostasis”), published in Cell Reports, offers 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, noted Antonis Hatzopoulos, Ph.D., associate professor of medicine and cell and developmental biology. "People thought that the same heart you had as a young child, you had as an old man or woman as well," he explained.
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.
Dr. Hatzopoulos and colleagues 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 novel methods to track cells in a mouse model, they have 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.
“Endothelial-derived cardiac progenitor cells were localized in the arterial coronary walls with quiescent and proliferative cells in the media and adventitia layers, respectively,” wrote the investigators. “Within the myocardium, we identified labeled cardiomyocytes organized in clusters of single-cell origin. Pulse-chase experiments showed that generation of individual clusters was rapid but confined to specific regions of the heart, primarily in the right anterior and left posterior ventricular walls and the junctions between the two ventricles. Our data demonstrate that endothelial cells are an intrinsic component of the cardiac renewal process.”
The finding that coronary arteries house a cardiac stem cell niche has interesting implications, according to Dr. Hatzopoulos. Coronary artery disease, the number one killer in the U.S., would impact this niche.
"Our 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," he said." It looks like the same endothelial system generates myocytes 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, he added.