Mechanisms of particulate matter-mediated cardiopulmonary toxicity in heart failure

This Pilot Project was used to support research to determine the biological mechanisms underlying cardiac toxicity due to the exposure to particulate matter (PM). Prior data from this lab suggested that PM-mediated cardiac toxicity involves pollution-induced inflammatory lung injury, increased lung vascular leakage, and the subsequent release of oxidative stress and inflammatory mediators that result in hypoxemia and increased blood coagulability. In addition, recent animal studies in this lab supported prior epidemiologic data implicating the exaggerated pulmonary endothelial barrier dysfunction, linking PM exposure and cardiac responses. Specifically, the outcomes from this Pilot Project indicated that changes in increased pulmonary and systemic endothelial integrity disruption worsen heart failure and increase the likelihood of fatal cardiac arrhythmias. The electrophysiological and genomic studies conducted by Dr. Wang suggested that PM components impose a dramatic effect on ion channel function and expression within the ventricular myocardium. These data lead to the formulation of a highly novel mechanistic hypothesis that PM-exacerbated cardiac arrhythmias involve multi-organ dysregulation superimposed upon a susceptible, predisposed cardiac phenotype (heart failure).