The molecular basis for contraction in normal arterial smooth muscle and for the motility of modified arterial smooth muscle cells in atherosclerotic lesions in not well understood. The proposed study is an investigation of the actin-myosin-regulatory-protein complex and its constituent proteins from the arterial media using biochemical and biophysical techniques including electrophoresis, ultracentrifugation, adenosine triphosphatase (ATPase) assays, and an in vitro actomyosin streaming system as an assay of biological activity. Myosin from normal arteries will be further characterized to determine the specific function of its subunits and to analyze the effect of various parameters that influence the biological activity of the ATPase. The calcium sensitive proteins which regulate smooth muscle contraction will be isolated and their regulatory properties investigated in detail. Contractile proteins from proliferating atherosclerotic lesions will be studied to determine the nature of molecular changes in these proteins which may accompany the disease. An attempt will be made to produce and then to reverse chemically these changes in smooth muscle cells in culture. This research should increase our understanding of contraction in smooth muscle and of motility in the disease state; but, more importantly, it may shed new light on the nature of atherogenesis.
NIH ExPorter
NIH ExPorter