Date on Master's Thesis/Doctoral Dissertation

8-2016

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Conklin, Daniel

Committee Member

Bhatnagar, Aruni

Committee Member

Hoyle, Gary

Committee Member

Myers, Steven

Committee Member

Wise Sr., John

Author's Keywords

air pollution; cardiovascular disease; PM2.5; endothelin-1; pulmonary oxidative stress; cardiovascular toxicology

Abstract

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In mice, the expression of the ET-1 system in the cardiopulmonary tissues changed significantly with exposure, with changes varying between exposure conditions. A potentially protective effect was seen in the lungs of ecSOD-Tg animals. These data suggest that ET-1 plays an important role in the vascular response to PM2.5 exposure.

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