Date of Award

Spring 2017

Degree Name

Master of Science in Engineering

Department

Chemical and Paper Engineering

First Advisor

Dr. James R. Springstead

Second Advisor

Dr. Andro Mondala

Third Advisor

Dr. Kalyana Pingali

Fourth Advisor

Dr. Brian Young

Keywords

Heart disease, lipids, inflammation, atherosclerosis, endothelial

Access Setting

Masters Thesis-Abstract Only

Restricted to Campus until

4-15-2027

Abstract

Coronary heart disease is now one of the leading causes of death in men and women in the United States. 5, 6 epoxyisoprostane (EI), a degradation product of the proinflammatory phospholipid, PEIPC, has been proven to downregulate monocyte chemotactic protein-1 (MCP-1) in human aortic endothelial cells (HAECs). Our central hypothesis is that EI binds one or more proteins in endothelial cells, an initial event leading to the downregulation of monocyte recruitment. To test this hypothesis, candidate proteins GRP78, VEGFR2, and EP2 were inhibited by siRNA in HAECs, and effects on MCP-1, inflammatory (IL-8), and oxidative stress (HO-1) gene expression in HAEC were measured with real-time PCR. The knockdown of VEGFR2 had the greatest effect, substantially inhibiting downregulation of MCP-1 and upregulation of IL-8 by EI. However, the data suggests that both GRP78 and VEGFR2 may be actively involved in this regulation, while results with EP2 knockdown remain inconclusive. Additionally, I compared the regulation of these genes by EI with other oxidized fatty acids, including a isoprostane, a neuroprostane, and a neurofuran. These lipids each showed unique regulation properties in HAEC and these results may guide the development of future therapeutics and understanding in the regulation of inflammation.

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