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THE MECHANISM OF PARTICULATE MATTER (PM)-ASSOCIATED ZINC IN CARDIAC INJURY IN WISTAR KYOTO RATS.
Impact/Purpose:
This project will provide mechanistic information on the role of PM-associated zinc in myocardial injury in rats prone to cardiovascular disease. Using fugitive emission samples from power plants and ambient air samples containing zinc, this project will examine the role of atmospheric PM-associated zinc as a potential causative agent in cardiovascular injury. Specifically, this work supports efforts to (1) Identify the role and the mechanisms of zinc as a causative constituent of PM in myocardial injury in susceptible rat model; (2) Characterize the role of zinc in myocardial injury in WKY rats.
Description:
We have recently found that inhaled combustion particulate matter (PM) with leachable zinc causes myocardial damage without significant pulmonary inflammation or remodeling; this damage is histologically demonstrable in Wistar Kyoto (WKY) rats. Cardiac injury from PM exposure can not be readily distinguished in Sprague Dawley or Spontaneously Hypertensive rats as unexposed rats demonstrate focal cardiac inflammation. Zinc is ubiquitously detected in the atmospheric PM, and is likely emitted from power plants. When bioavailable, it can be transported to the heart via the circulation. We hypothesized that myocardial damage may be caused by bioavailable PM-associated zinc and further that cardiomyocyte injury will involve activation of cell signaling disturbance in calcium homeostasis, ion channels, and mitochondrial respiration. To address this hypotheses, WKY rats will inhale zinc sulfate or emission PM primarily containing bioavailable zinc. The dose-response, time course and the nature of myocardial inflammation/fibrosis will be characterized. Specific aims include: (1) Characterize cardiac injury in rats exposed to inhaled zinc versus zinc containing emission particles in WKY rats. (2) Determine the mechanism by which zinc may induce myocardrial injury and evaluate the role of cell signaling ion channels and mitochondria in the hearts of zinc-exposed WKY rats. To confirm that ambient PM-associated zinc as a causative component of cardiac injury, we will use ambient PM samples rich in zinc and also tire and brake particles.