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EFFECTS OF PARTICULATE MATTER (PM) ON CARDIAC CELLS
Impact/Purpose:
These studies should provide a better understanding of the cellular and molecular mechanisms by which particulate matter (PM) causes cardiac dysfunction. As such they will provide biological plausibility to the epidemiology, clinical, and animal studies which show PM-induced cardiac dysfunction. Specifically, this work will support efforts to (1) Identify mechanisms of toxicity for PM constituents/ sources; (2) Describe the acute effects of PM derived metals on cardiac tissue and cells from healthy animal models; (3) Describe the acute effects of PM derived metals on cardiac tissue and cells from healthy animal models; and (4) Develop methods for studying mechanisms of effects in tissue from human subjects exposed to PM.
Description:
Although epidemiology studies, clinical studies, and animal studies indicate that particulate matter (PM) can affect cardiac function, there is no real understanding of the underlying cellular, biochemical, and molecular processes response for PM-induced cardiac dysfunction. It is possible that PM or some of its components may leave the lung and directly affect cardiac tissue; it is also possible that PM may induce the lung or other organs (e.g. liver, endothelial cells) to produce compounds (e.g. cytokines, acute phase proteins) which in turn affect cardiac tissue. This project uses cultured cardiac myocytes as a model system to assess whether soluble components of PM or PM-induced plasma components affect ion channels, gap junctions, and other molecules used by the myocytes to transmit electrical signals. The hypothesis is that PM induces arrhythmias, changes in heart rate variability, and repolarization changes by affecting the proteins responsible for transmitting electrical signals in the heart. Preliminary experiments are using model soluble PM components to define exposure conditions and suitable end points to measure. Subsequent experiments will focus on the use of soluble components of ultrafine, fine and coarse PM collected in Chapel Hill, NC, as well as serum components collected from rats exposed to PM.