Grant: Operating Grant

Understanding the intracellular mechanisms by which growth factors produce their effects in endothelial cells is an important aspect of vascular biology. Endothelial cell are intimately involved in formation of new blood vessel, termed angiogenesis, and in the control of vascular tone. Vascular endothelial growth factor (VEGF) is an important factor for endothelial cells as it promotes their proliferation, survival and angiogenesis. Angiogenesis is deregulated in several cardiovascular pathologies such as atherosclerosis and cardiac infarct. In this proposal, we will attempt to modulate the ability of VEGF to control angiogenesis by altering cellular processes that affect the degradation and stability of VEGF receptors in endothelial cells. Furthermore, we will investigate how the release of nitric oxide, a critical factor produced by endothelial cells in response to VEGF, is affected by the modulation of VEGF receptor degradation. Defining new approaches to modulate the effects of an essential factor for the formation and maintenance of blood vessels will hopefully open the way to the identification of novel therapeutic targets in cardiac and vascular diseases.