Epidemiological studies consistently show a positive relationship between airborne particulate matter (PM) and increased morbidity and mortality from cardiovascular disease. The mechanisms underlying PM-associated cardiovascular toxicity are largely unknown. Dr. Kurt Varner's research group has discovered aromatic chlorinated hydrocarbons combine with metal-containing PM to form surface stabilized, environmentally persistent free radicals (EPFRs). They have shown that EPFRs:
These data suggest EPFR-mediated OS and inflammation underlies the observed functional deficits and increased vulnerability to I/R injury. Cellular homeostasis in response to OS and inflammation is maintained by the balanced activation of tier 2 antioxidant genes via the transcription factor, Nrf2, and the proinflammatory NFκB pathway. Dr. Varner hypothesizes that: EPFR-induced oxidative stress and inflammation enhance cardiac injury and dysfunction by "tipping the balance" between the antioxidant Nrf2 and the proinflammatory NFκB pathway to favor NFκB. To test this hypothesis, he proposes 3 specific aims:
This research relies on the interdisciplinary strengths of the LSU-SRP. Lung tissue from this study is being analyzed for OS and inflammation by Dr. Stephania Cormier. Dr. Wayne Backes is examining P450 expression and function with respect to OS in the cardiac tissue samples. Dr. Varner is also drawing heavily on the expertise and analysis performed by the Oxidative Stress Core, while all of the samples tested will be generated by the Materials Core.