Vascular endothelium plays a key role in control of cardiovascular function by synthesis and release of vasoactive substances including a potent vasodilator, nitric oxide (NO). Reduced biosynthesis or biological activity of NO is a major molecular mechanism underlying endothelial dysfunction. Our interest has been focused on mechanisms responsible for development of endothelial dysfunction as well as identification of therapeutic targets for protection of endothelium and preservation of NO biosynthesis. Maintenance of the endothelial surface integrity requires constant replacement of damaged or dead endothelial cells. Circulating endothelial progenitor cells (EPCs) repair injured endothelium thereby preventing development of endothelial dysfunction, an initiating event in pathogenesis and progression of atherosclerosis. We are studying biology of EPCs as well as their potential as gene delivery system for genetic modification of cerebral and peripheral circulation. The long-term goal of our program is to develop new endothelium targeted strategies in prevention and treatment of major vascular diseases including stroke and myocardial infarction.