Epidemiological evidence indicates that acute pulmonary exposure to airborne pollutants such as particulate matter (PM) increases the risk of pulmonary and cardiovascular morbidity and mortality. This implies that PM affects extra-pulmonary tissues, as evidenced by the occurrence of cardiovascular dysfunction on high pollution days. Furthermore, Federal Criteria Documents for PM have provided a wealth of evidence demonstrating PM dependent effects on the cardiovascular system. However, despite its obvious importance in regulating the delivery of cells and molecules to all tissues, and in the etiology of most cardiovascular diseases, the Principal Investigator's laboratory conducts the lone investigations that explore how systemic microvascular function is affected by pulmonary PM exposure. The overall aim of this project is to determine if there is a true causal link between the inflammatory events that follow PM exposure and the disruption of endothelium-dependent dilation. The central hypothesis is: Inflammatory mechanisms govern the systemic microvascular dysfunction that follows ultrafine PM exposure, and the severity of this dysfunction is augmented in clinically relevant populations. Intravital microscopy and isolated vessels will be used to test this hypothesis in the spinotrapezius muscle, bone marrow, and subendocardial circulations of rats and mice exposed to diesel exhaust particles (DEPs) or ultrafine titanium dioxide. The role of gender and age in determining the severity of these effects will also be studied. Various in vivo and in vitro techniques will be used to measure microvascular reactivity after PM exposure, and to characterize pathological changes at this crucial level of the circulation. DEPs are mobile source emission air pollutants representative of particles that humans are exposed to on a regular basis. Ultrafine titanium dioxide is a commonly used nanoparticle found in cosmetics, paints and various protective coatings. A better understanding of how these particles affect remote microvascular function will provide mechanistic insight into pathologic changes that contribute to cardiovascular morbidity and mortality. Moreover, these studies may provide a biological basis for the epidemiological associations between air pollution and cardiovascular dysfunction. A fundamental understanding of these mechanisms is vital to the prevention and treatment of life-threatening cardiovascular events, and will contribute to control strategy development.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZES1-JAB-C (R1))
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Nadadur, Srikanth
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West Virginia University
Schools of Medicine
United States
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