The aim of this research is to develop an understanding of the chondroitin sulfate proteoglycan NG2's role in normal and pathological physiology of aortic smooth muscle cells (SMC). Vascular SMC play an integral role in the development and maintenance of the cardiovascular system; yet, little is known about the complex regulation required for their diverse functions (i.e., proliferation, migration, contractility, extracellular matrix deposition). Knowledge of the normal regulation of vascular SMC will contribute greatly to our perception of their role in vascular diseases. The proteoglycan NG2 may influence PDGF-AA stimulated biological actions in SMC. The use of SMC derived from the Spontaneously Hypertensive Rat, that express high levels of the alpha PDGF receptor, will allow indepth analyses of physical interactions between NG2 and the alpha receptor via crosslinking experiments, autophosphorylation and substrate phosphorylation by the alpha PDGF receptor. Additionally, studies will be done to quantify changes in SMC proteoglycan expression induced by growth factors and to determine any effects of other relevant molecules, such as interleukins,known to be important in pathological states. To complement the above-described studies, SMC clones not expressing NG2 will be derived from NG2-gene-knockout mice. Appropriate clones will be analyzed for differences in biological responses to growth factor stimulation.
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