Vascular proliferative diseases are characterized by abnormal smooth muscle cell (vsmc) proliferation, leading to failure of stent and bypass procedures and recurrent ischemia. The goal of this laboratory is understand the molecular and cellular mechanisms of vsmc growth regulation by cell cycle proteins. Towards this end, there are several lines of investigation: 1) expression and function of the Cip/Kip cyclin-dependent kinase inhibitors (CKIs), p27 and p21, in the vasculature; 2) the mechanisms by which p27 and p21 protect against vascular lesion formation in p27, p21 and p27/p21 null mice; 3) the role of p27 and p21 in atherosclerotic lesion formation; 4) the molecular mechanisms of heme oxygenase-1 function in arteries; 5) the regulation of p27 phosphorylation by the kinase, KIS; 6) the role of PRMT2 in regulation of Rb phosphorylation; and 7) gene expression profiling in normal and injured mouse and baboon arteries. Other collaborative projects include imaging modalities in the vasculature and adenoviral gene transfer with VEGF to promote peripheral angiogenesis. Taken together, these studies define the molecular function and regulation of cell cycle proteins in vascular tissues. On the basis of these molecular studies, novel therapeutic approaches to vascular proliferative diseases are being developed.
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