Defense Date

2007

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Obstetrics & Gynecology

First Advisor

Dr. Scott W. Walsh

Abstract

Obesity is a known risk factor for preeclampsia, but the reason for this risk is unknown. We sought to demonstrate how obese individuals are predisposed to preeclampsia by mechanisms involving inflammation and the innate immune system. First, we used immunohistochemical studies to identify neutrophil infiltration, NF-κB activation and COX-2 expression in vascular tissue of obese women. We then demonstrated similar neutrophil infiltration and vascular inflammation in preeclamptic women.We used in vitro experiments to test if neutrophils and their products, reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNFα) can activate NF-κB and cause expression of its inflammatory products, COX-2, thromboxane (TX) and IL-8. Co-culture of neutrophils or treatments of ROS or TNFα caused activation of NF-κB and expression of COX-2, TX and IL-8 in vascular smooth muscle cells.This investigation is the first to demonstrate activation of NF-κB and expression of COX-2 coincident with neutrophil infiltration in systemic vascular tissue of obese and preeclamptic women. These data implicate neutrophils as a cause of vascular inflammation. They also suggest that if an obese woman's vasculature was in an inflamed state she is at increased risk for preeclampsia when exposed to the additional burden of oxidative stress and neutrophil activation imposed by the placenta, causing her to develop vascular dysfunction and clinical symptoms of PE (hypertension and edema).

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

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