| The goal of this project was to investigate the relationship between hemodynamic forces and endothelial gene expression, especially in relation to atherosclerosis. Using in vitro cell culture models of steady laminar and disturbed flow, we established that matrix metalloproteinase-9 is differentially regulated in endothelial cells by the local hemodynamic regimen. The second facet of this project was the creation and validation of an in vivo murine model of disturbed aortic hemodynamics. Following the introduction of an aortic constriction, biochemical and histochemical analysis revealed focal changes in vascular permeability, inflammation, and gene expression indicative of early atherosclerotic lesion development. We thus generated a murine model for future investigations studying the development and progression of atherosclerotic lesion in relation to a disturbed flow environment. The final accomplishment of this project was the development of a protocol for isolating and culturing primary murine aortic endothelial cells. By allowing future investigations to utilize the identical genetically engineered animals for in vitro studies, these cells will function as a platform technology to allow us and others to elucidate the role of the endothelium in complex pathologies such as atherosclerosis. These advances contribute to our understanding of the role of mechanophysical signaling in cardiovascular disease. |
