Atherosclerosis is a disease process of the large arteries, the major complication of which lead to the development of ischemic heart disease, which accounts for a significant proportion of adult mortality in the United States today. We propose to study the major cellular component of the normal and diseased vessel wall and the smooth muscle cell. We propose to develop further a panel of smooth-muscle cell specific monoclonal antibodies specific to muscle-specific cytoskeletal protein isotypes and to particular subsets of smooth muscle cells that define particular states of differentiation, proliferation, or site of origin. These antibodies will then be used via immunocytochemistry to analyze the SMC in vivo of human, monkey, and rabbit, looking for variations with respect to site of vessel and location within the vessel wall. For human specimens, a time study of SMC embryonic development in the aorta will be undertaken. Smooth muscle cells from these and other sources will be grown in culture, and the following cell culture variables will be analysed, looking for their effect upon reactivity via immunocytochemistry and immunoblotting with the monoclonal antibody panel: a) passage number; b) growth density; c) cytoskeletal protein phosphorylation; d) growth fraction; e) platelet-derived growth factor (PDGF) receptor status; and f) PDGF production. It is thus anticipated that through this analysis of SMC phenotype important structure-function relationships can be characterized and in vivo and in vitro variables can be interrelated into a meaningful scheme.
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