Grant: Project Grant

Endothelial cells (ECs) are intimately involved in angiogenesis, the formation of new blood vessels from preexisting ones. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor and its administration has been shown to increase the development of new vessels in ischemic tissues and to be essential for the formation of blood vessels inside cancerous tumors. A better understanding of the angiogenic process and of the intracellular signaling molecules involved in its regulation could allow for the development of new therapeutic approaches to favor the formation of new blood vessels in ischemic tissues or, inversely, interfere with aberrant vessel growth in the retina or in tumors. An essential event for the induction of angiogenesis is the increase in permeability of the vasculature to blood macromolecules. The opening of intercellular contacts between ECs initiates the angiogenic process and detachment of ECs allows them to migrate to form a vascular network in an area deprived of oxygen. The overall objective of our research program is to understand intracellular signaling events in ECs that control vascular development and angiogenesis. We will investigate if polarization of ECs is modified by nitric oxide, which would affect angiogenesis. First, we will define if the release of nitric oxide (NO) controls the migration of cells. We will also determine if NO acts directly on a protein localized at cell-cell contact points, beta-catenin, to alter its function. Finally, we will determine the role of NO in a mouse model of vascular retinopathy. A better understanding of the molecular events that control angiogenesis will help in the development of novel therapeutic approaches where the formation of new vessels is central to disease progression such as in ischemic tissues and vascular retinopathies.