Study on the Upregulation of Myocardin Gene Expression in Vascular Smooth Muscle Cells during Cell Cycle Arrest

As our people's dietary habits become more westernized in Taiwan, the atherosclerosis-related cardiovascular diseases appear to more significantly threaten our health and life. Multiple cellular events are involved in the development of atherosclerotic lesions. Among them, the altered phenotype and the functional change of vascular smooth muscle cells during the development of atherosclerosis significantly determine the fate of atherosclerotic plaque. Because of its pivotal role in the pathogenesis of atherosclerosis and other vessel diseases such as restenosis after balloon angioplasty and other surgical procedures, the smooth muscle cells have become an important target for pharmacological therapy. The purpose of therapeutic treatment is to interfere with the transition of smooth muscle cells from a 「contractile」 to a 「synthetic」 phenotype, or more effectively, even to reverse the phenotype of vascular smooth muscle cells in the diseased vessel from 「synthetic」 back to 「contractile」phenotype as in the normal media layer of vessel. A deeper knowledge certainly will help to widen our understanding of vascular smooth muscle cell differentiation, which will assist in the development of new and improved methods for prevention and treatment of major vascular diseases. Myocardin, a novel cardiac and smooth muscle-specific transcriptional factor for serum response factor (SRF), has been discovered recently. The complete block of vascular smooth muscle development in myocardin-/-embryos demonstrates that myocardin is an essential activator of smooth muscle differentiation program in vivo and that no other factor can substitute for this promyogenic function. The gene expression of myocardin was found to correlate well with the phenotypic modulation of vascular smooth muscle cells in vitro. Data accumulated so far provide direct evidence that myocardin plays an important role in modulation of smooth muscle gene expression by functioning to push non-SMC to SMC-like phenotype. Except exploring the myocardin functions, the effort to find out the regulation of myocardin itself in vascular smooth muscle cells is also another important issue. In our preliminary data, we have demonstrated the highly increased gene expression of myocardin in VSMCs during cell cycle arrest. In the present proposal, we plan to investigate the potential regulatory mechanisms responsible for the regulation of myocardin gene expression in human vascular smooth muscle cells

Project ID:PC9412-0010
External Project ID:NSC94-2320-B182-055