Title of Abstract
The overall goal of the laboratory is study how various humoral and mechanical factors modulate vascular inflammatory responses as they pertain to the development of atherosclerosis, angiogenesis and hypertensive vascular disease. Specifically, we study the effects of angiotensin II, advanced glycation end products and wall strain on these processes. The specific projects underway include:
1) The Role of Angiotensin II in the Pathogenesis of atherosclerosis. In this project we are focusing on the contribution of oxidative stress as a signaling mechanism in atherogenesis. We are also exploring the functional contributions of specific candidate genes.
2) Mechanical Strain and Vascular Inflammation. We have previously shown that when cyclic strain is applied to vascular smooth muscle cells, it induces the production of reactive oxygen species and an upregulation of proinflammatory genes. We are currently studying the effects of cell phenotype on this response. In addition, we are interested in the mechanical properties of vascular cells of different phenotypes.
3) Mechanisms of Angiogenesis. Angiogenesis is a complex process involving the growth and arterialization of new blood vessels. We are currently using several animal models to define the roles of osteopontin (an extracellular matrix protein) and angiotensin II in this process.
4) Advanced Glycation Endproducts (AGEs) and Vascular Inflammation. AGEs are produced after extended periods of hyperglycemia (high blood sugar). We have shown that AGE?s cause a proinflammatory response in the vessel wall. We are currently looking the mechanisms of this response and the role of a specific receptor (RAGE) for AGE?s.
5) Endothelial Progenitor Cells and Vascular Disease. In this project we are developing new methodologies to isolate and culture human endothelial progenitor cells from the peripheral circulation. These efforts are being coordinated with several clinical trials now underway at Emory. In addition, we are integrating these studies with animal models of vascular disease to further explore the role of circulating endothelial progenitor cells in vascular repair and inflammation.