Vascular smooth muscle plays a pivotal role in the physiology and pathology of the blood vessels. Alterations in the contractile properties and phenotype of the smooth muscle cell have been implicated in such common vascular disease processes as atherosclerosis and hypertension. In spite of its central role in vascular pathophysiology very little is known about the contractile apparatus and its regulation. A detailed understanding of the molecular structure, heterogeneity and genetic regulation of the contractile proteins is required before structure/function correlations can be established. In order to determine some of the biochemical correlates defining smooth muscle physiology and pathology, we propose to elucidate the molecular structure, heterogeneity and genetic regulation of the vascular smooth contractile proteins using recombinant cDNA methods. We will make use of the cultured vascular smooth muscle system which is an excellent model for studying the phenotypic modulation of smooth muscle cells from a contractile to synthetic state. The specific objectives to be pursued are: (1) isolation and characterization of recombinant cDNA clones for major contractile proteins; (2) analysis of multi-gene families and isoforms for specific contractile proteins; (3) contractile protein gene expression in vascular development and in different vessel types; (4) gene expression in cultured smooth muscle cells and in atherosclerosis animal models. We anticipate that these studies should provide direct insight into the mechanisms governing vascular function and modulation at the subcellular level.
