Date on Master's Thesis/Doctoral Dissertation

5-2013

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Environmental and Occupational Health Sciences

Committee Chair

Bhatnagar, Aruni

Author's Keywords

Environmental cardiology; Vascular progenitor cells; Cardiovascular disease risk; Acrolein; Roadway proximity; Environmental epidemiology

Subject

Cardiovascular system--Diseases; Environmentally induced diseases; Particles--Health aspects

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the U.S., and its prevalence is predicted to increase through 2030. Acute and chronic exposure to fine particulate matter (PM2.5) and traffic pollution is positively associated with cardiovascular morbidity and mortality. It has been recently shown that exposure to elevated levels of combustion pollutants including tobacco smoke and PM2.5 is associated with decreased circulating levels of vascular progenitor cells (VPCs), angiogenic cells that participate in vascular repair and regeneration. Several investigators have reported that decreased VPC levels is associated with an increase in CVD risk and endothelial dysfunction (a decrease in vasodilatation), which is a key feature in atherosclerosis. Nevertheless, the mechanisms by which combustion pollutants affect VPC levels remains unclear, and the contribution of pollutant-induced VPC depletion to elevated CVD risk has not been assessed. This dissertation investigates how exposure to environmental pollution is associated with VPC levels in a population with increased CVD risk. The first chapter assesses 15 phenotypically distinct VPC populations with different angiogenic potential to describe the association between VPC levels and CVD risk factors, the Framingham Risk Score (FRS), and markers of thrombosis (fibrinogen and platelet mononuclear cell aggregates) and inflammation (high sensitivity C-reactive protein (hsCRP)). The second chapter describes the association between acrolein exposure (a combustion pollutant) and VPC levels, a novel assessment in human subjects. To understand the vascular effects of exposure to traffic pollution, the association between roadway proximity and VPC levels was evaluated in the third chapter. Together, these investigations suggest that VPCs may be a mechanistic link between CVD risk and environmental exposures. Results from these investigations may drive future mechanistic explorations, as well as targeted diagnostic examinations and prevention interventions.

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