Date of Award

7-9-2009

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Daniel Goldstein

Abstract

As our understanding of atherosclerosis has become more sophisticated, a picture of the disease has emerged which emphasizes the role of inflammation in the pathogenesis of the disease, including signaling cascades mediated by toll-like receptors (TLRs). Data has also emerged suggesting that the process of aging plays an important role in atherogenesis, through pathways at least partially mediated by changes in the function of vascular smooth muscle cells. The purpose of this study was to elucidate the role that aging might play in the TLR-dependent innate immune response of vascular smooth muscle. Ex vivo cell and tissue culture models were used, with cytokine and chemokine production in response to stimulation with TLR agonists measured by ELISA assays. Our study demonstrated differences between aged and young cells and tissue specimens in the production of the pro-inflammatory cytokines interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1), with greater production of IL-6 and less production of MCP-1 seen in the aged specimens than in the young specimens. We discuss these results in the context of aging-related alterations in the innate immunity of vascular smooth muscle.

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