The Role of Lysophosphatitic Acid in the Growth Factor Signal Transduction Cascades of Rat Aortic Smooth Muscle Cells
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Research has demonstrated that the release of growth factors cause cell mitogenesis and cell hypertrophy, and as a result have been implicated in the development of several cardiovascular diseases such as atherosclerosis, hypertension, and restenosis. Platelet derived growth factor (PDGF) plays a role in several of these pathologies via stimulation of the signal transduction pathway. It has been shown that angiotensin II is capable of stimulating the pathway characteristic of platelet deriyed growth factor. Further research pointed to lysophosphatitic acid, LPA, as a possible mediator of the activities of angiotensin II. Investigation of LPA involved precipitation of the Shc protein in rat aortic smooth muscle cells treated with LPA. Poly vinyl difluoride blots generated via gel electrophoresis were probed with antibodies specific to phosphorylated Shc and growth factor receptor binding protein 2 (GRB2). Analysis demonstrated LP A capable of stimulating signal transduction to some degree, less than that of platelet derived growth factor or angiotensin II. Further investigation showed that LP A is incapable of stimulating the 𝛽-PDGF receptor phosphorylation, which supports the notion of a different mediator for angiotensin II. Investigation of phospholipase D and phosphatitic acid showed that phospholipase D initiates signal transduction, but insignificant levels of phosphorylated Shc and GRB2 were detectable in cells stimulated with phosphatitic acid.