New Scholar Award in Aging
Jay M. Edelberg, Ph. D.
Cornell University

Regulation of Senescent Angiogenic Potential

The incidence of ischemic heart disease increases with advancing age. Unfortunately, the physiologic response to cardiac myocardial ischemia, the angiogenic development of new blood vessels, is decreased in the elderly population as demonstrated by both clinical and experimental studies.

The focus of our laboratory is to understand the biological basis for the depression of angiogenic activity in the aging heart. Previous studies have revealed that these age-dependent differences in cardiac angiogenesis correlate with the diminished capacity of cardiac microvascular endothelial cells to migrate into new capillary beds. We hypothesize that the senescent-associated depression in cardiac angiogenic potential may be due to altered endothelial cell regulation. To this end, we are studying the senescence-associated changes in the communication pathways governing cardiac endothelial cell activity. We previously demonstrated that cardiac microvascular endothelial gene expression is, in part, regulated by the surrounding cardiac myocytes. Recently, we showed that this communication between cardiac microvascular endothelial cells and cardiac myocytes is mediated by platelet-derived growth factor (PDGF) AB and the PDGF a receptor. The PDGF-dependent pathway induces the endothelial expression of critical angiogenic components, including vascular endothelial growth factor and its receptor, Flk-1. These findings, in conjunction with previous studies by others that have revealed decreased levels of PDGF isoforms and receptors in the aging heart, suggest that alterations in this cardiac microvascular communication may contribute to the depressed angiogenic potential in the senescent heart.

Our present research studies the changes in the microvascular communication in the aging murine heart. Our goal is to identify the molecular and cellular pathways that may contribute to the depression in senescent cardiac endothelial angiogenic activity. Moreover, the results of these studies may offer a foundation for the development of novel cardiovascular therapeutic approaches specifically targeted at the aging heart.

Contact Dr. Edelberg.