The general objective of this revised Program Project application is to define mechanisms whereby men are at greater risk for coronary artery disease than women. Two of the original projects (I and III) have been withdrawn. Individual projects address the following areas: (II) sex differences and steroid effects in responses to experimental acute myocardial ischemia; (IV) effects of gonadal hormones on the development of coronary atherosclerosis in experimental cardiac transplantation, (V) predictive value of urinary thromboxane metabolites in myocardial infarction in men and women; and VI) sex steroid mechanisms of vascular reactivity of the internal mammary artery. The general approach used in the animal models is to delineate fully male and female responses in the systems being studied, determine the role of androgens ad estrogens in the sex differences, demonstrate the mechanisms involved in the sex differentiated processes and thus develop insight into therapeutic approaches to reduce the higher incidence of coronary events in men and postmenopausal women. Project V is an outgrowth of our earlier work on the role of sex and eicosanoids in cardiovascular disease and is a study of the predictive value of urinary thromboxane for myocardial infarction in men and women presenting with chest pain. Project VI is a new project and is directed to mechanisms and employs as a model, the internal mammary artery which is used extensively as a coronary artery bypass conduit. This Program focuses current research by investigators with a history of fruitful collaboration. The them of the Program, sex differences in coronary artery disease, will be investigated using markedly different approaches, but with a high degree of integration between the different projects. Two cores are included to facilitate the execution of the proposed projects: A) Administrative Core, and B) Animal Core. The animals to be used include rats, rabbits and pigs.
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