Research Abstract:
Research in this physiology laboratory focuses on the molecular responses of the arterial wall to acute injury. We have shown that inhibition of coagulation proteases including factor Xa and tissue factor/factor VIIa complex are particularly effective to attenuate thrombosis and neointimal thickening after angioplasty-like injury in experimental animals. Current studies are designed to determine the time course and mechanisms of procoagulant activity on the surface of the injured vessel. Another aspect of this research has been to establish a reproducible preparation of angioplasty-like overstretch injury in the carotid arteries of mice to address the role of signaling pathways involved in stimulating vascular smooth muscle cells to proliferate and migrate into the developing neointima. Current studies are designed to determine the effect of knockouts of integrin receptors, G-proteins, and inflammatory receptor proteins on neointimal thickening after arterial injury. We are also interested in the role of inflammatory cells in inducing a more robust neointimal response after angioplasty in the diabetic state. Current experiments are testing the hypothesis that changes in diabetic monocyte membrane phospholipids facilitate entry into the vessel wall promoting atherogenesis.
Selected Publications:
Choi ET, Khan MF, Leidenfrost JE, et al. Beta3- integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice. Circulation 2004 109:1564-1569.
Morawski AM, Winter PM, Crowder KC, et al. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 2004 51:480-486.
Leidenfrost JE, Khan MF, Boc KP, et al. A model of post-angioplasty intimal hyperplasia and arterial remodeling in mice. Am J Pathol 2003 163:773-778.
Zhang S, Ren J, Khan MF, et al. Grb2 is required for development of neointima in response to vascular injury. Arterioscler Thromb Vasc Biol 2003 23:1788-1793.
Last Updated: 09/08/2006 |