We have hypothesized that smooth muscle cells within the vascular wall may be a diverse population and that different smooth muscle cell types may make unique contributions to the disease process. this project aims to characterize vascular smooth muscle cell diversity in arteries as a function of development and injury. We will utilize differential cloning to isolate genes which are unique to particular lineages of smooth muscle cells, and determine expression patterns and functions of these genes in cultured, cloned cells as well as in vivo. Cells which show stable differences based on gene expression patterns will also be assessed for differences in growth properties and culture requirements. We will also explore the possibility that distinct smooth muscle cell types may be interconvertible, and that growth factors and/or extracellular matrix may regulate the conversion process. Finally, we propose to study the function of a protein, osteopontin, which we have recently discovered during the differential cloning of genes expressed by cells associated with formation of the neointima. Identification and characterization of distinct smooth muscle cell phenotypes which make up the normal and diseased artery wall will be essential to devise efficient strategies to prevent and/or correct abnormal vascular cell growth.
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