Date of Award

8-2015

Degree Name

Master of Science in Engineering

Department

Chemical and Paper Engineering

First Advisor

Dr. James R. Springstead

Second Advisor

Dr. Kalyana Chakravarthy Pingali

Third Advisor

Dr. Brian Young

Access Setting

Masters Thesis-Open Access

Abstract

Low-density lipoprotein particles in blood plasma invade the endothelium and become oxidized, creating risk of CHD associated with atherosclerosis, the main underlying condition in coronary heart disease. Oxidation products of the phospholipid 1-palmitoyl- 2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC) are bioactive components of minimally oxidized LDL that stimulate endothelial cells that line the artery, leading to monocyte binding and atherosclerosis. It is hypothesized that the regulation of the monocyte recruitment pathway by these oxidized phospholipids is mediated by the binding of OxPAPC to one or more mediating proteins. Human recombinant VEGFR2, GRP78, and EP2bind to OxPNB, a biotinylated analog of OxPAPC, demonstrated using Western blotting. Binding of OxPNB to these proteins in cells remains inconclusive and will need to be investigated in further studies. OxPAPC upregulates IL-8, HO-1 and MCP-1 in HAECs as demonstrated with RT-PCR, agreeing with previous studies. Gene knockdown of GRP78 and EP2 by siRNA yields substantial inhibition of the inflammatory response, including MCP-1 and IL-8. Knocking down VEGFR2 did not inhibit the upregulation of MCP-1 and IL-8. These experiments and future studies on the mechanism of Ox-PAPC-catalyzed inflammation in HAEC will contribute to the development of a new and more effective treatment for heart disease.

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