Recent epidemiologic evidence suggests that moderate and low radiation doses to the heart may result in a moderate, but significant increase in cardiovascular mortality. So far, the pathogenesis of radiation induced heart disease has not been studied in detail. Pathohistologic studies suggest that microvascular damage plays a crucial role in the development of radiation induced cardiovascular disease. In addition, radiation may increase atherosclerotic lesions in the coronary arteries. The aim of this collaborative research project is to elucidate the pathogenesis of early and late alteration in the microcirculation of the heart and of atherosclerotic lesions in arteries after exposure to low radiation doses in comparison to high radiation doses. A major goal will be the investigation of early molecular, proinflammatory and prothrombotic changes as well as perfusion alteration, cardiac cell integrity and immunologic influences. To achieve this goal, in vivo as well as ex vivo and in vitro studies will be performed. A central component of the project will be the local irradiation of the heart with subsequent isolation of cardiomyocytes and cardiac endothelial cells to provide all participating groups with the same biological material for further study. In addition, structural, morphological and molecular studies will be complemented by functional assays and imaging methods.
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