The Role and Regulation of Osteopontin in Hypertension Related Remodeling and Inflammation of the Aorta
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The arterial wall experiences elevated mechanical strain in the setting of hypertension, which leads to vascular inflammation and atherosclerosis. However, many of the underlying molecular mechanisms modulating this strain-dependent inflammation of the aorta are still largely unexplored. Therefore, the overall goal of this work was to analyze the specific role and regulation of the pro-inflammatory protein, osteopontin (OPN) in the aorta, in the context of hypertension. First, the expression and regulation of OPN in response to mechanical strain using an in-vitro system was evaluated. Two in-vivo models of murine hypertension were also used to determine if OPN expression was regulated via hydrogen peroxide in the setting of hypertension. Finally, we explored the contribution of OPN to the mechanical properties of the aorta under healthy and hypertensive conditions. Our results have shown that OPN is in fact up-regulated with mechanical strain in smooth muscle cells and in the aorta with hypertension via hydrogen peroxide. We have also shown that it plays an important role in mediating inflammation and remodeling of the aorta. Overall these results deepen our understanding of vascular inflammation, and have important implications in the future design of therapies and strategies aimed against the consequences of hypertension such as atherosclerosis.