The major purpose of this investigator-initiated multicenter cooperative study is to answer, utilizing modern pathobiological approaches, some key questions concerning the pathogenesis of human atherosclerosis in the USA. Aortas and coronary arteries from 15-35 years old males and females from multiple study sites will be examined to determine detailed characteristics of arterial changes observed in late childhood which may suggest potential progression to lesions commonly found in young adults. Our proposal will address these objectives by systematically evaluating a large number of coronary arteries and aortas from young persons succumbing suddenly and unexpectedly from accidental causes. Under standardized conditions, isolated fatty streaks, transitional lesions and fibrous plaques will be examined for 1) protein composition and lesion distribution of specific lipoproteins and glycosoaminoglycans in intimal lesions as well as in isolated arterial cells utilizing two-dimensional electrophoresis combined with immunospecific staining with monoclonal antibodies and peroxidase labeled lectins; 2) identification of cells found in each lesion type will be carried out using specific surface membrane markers, by the detection of humoral immune components at lesion sites with monospecific antibodies and by evaluating the role of immune complexes on lesion development 3) detection of viral antigens at lesion sites by immunohistological methods as well as in situ nucleic acid hybridization technology will be used to evaluate the potential role of viruses and/or their genomes known to produce latent or persistent infections on the initiation and/or progression to advanced atheroma; and 4) by developing probability maps for each age group of the occurrence of specific type lesions, attempts will be made to define average topological loci in relation to lesion severity, sex or race comparing lesion-prone vascular segments with those found to have low probability to develop atheroma in each age group. It is believed that such information, combined with those of the other centers participating in the overall USA protocol should provide much needed information regarding the evolution of the early stages of human atherogenesis as well as their potential clinical significance.
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