Date of Award

11-10-2006

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Alan Dardik

Abstract

I hypothesize that shear stress helps maintain the quiescent phenotype of vascular endothelium. I also hypothesize that changes in levels of shear stress facilitate alternations in endothelial cell activity consistent with an activated phenotype and the development of atherosclerotic vascular disease. Purpose #1: To assess the effects of aging on EC proliferation induced by SS Hypothesis: Orbital SS stimulates EC proliferation. Aged cells are less responsive to orbital SS and show less proliferation. Purpose #2: To assess the effects of aging on EC survival and apoptosis Hypothesis: Versus younger cells, aged cells have increased rates of apoptosis. Purpose #3: To assess the effects of aging on SS induced SMC chemotaxis Hypothesis: Aged EC are less responsive to orbital SS and induce less SMC chemotaxis versus younger cells. Purpose #4: To assess the effects of aging on Akt pathway activation with SS Hypothesis: Orbital SS activates EC leading to phosphorylation of Akt. Versus younger cells, aged cells are less responsive to orbital SS and show less stress induced phosphorylation of Akt.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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