Platelet-Derived Growth Factor-BB-Induced Suppression of Smooth Muscle Cell Differentiation

Previously, we demonstrated that treatment of postconfluent quiescent rat aortic smooth muscle cells (SMCs) with platelet-derived growth factor (PDGF)-BB dramatically reduced smooth muscle (SM) α-actin synthesis. In the present studies, we focused on the expression of two other SM-specific proteins, SM myosin heavy chain (SM-MHC) and SM α-tropomyosin (SM-αTM), to determine whether the actions of PDGF-BB were specific to SM α-actin or represented a global ability of PDGF-BB to inhibit expression of cell-specific proteins characteristic of differentiated SMCs. SM-MHC and SM-αTM expression were assessed by one- or two-dimensional gel electrophoretic analysis of proteins from cells labeled with [S]methionine, as well as by Northern analysis of mRNA levels. Synthesis of both SM-specific proteins was decreased by 50–709% in PDGF-BB-treated cells as compared with cells treated with PDGF vehicle. Treatment of cells with 10% fetal bovine serum, which produced a mitogenic effect equivalent to that of PDGF-BB, decreased SM-MHC synthesis by 40% but increased SM-αTM synthesis. SM-MHC and SM-αTM mRNA expression was decreased by 80% at 24 hours in PDGF-BB-treated postconfluent SMCs, whereas treatment with 10% fetal bovine serum did not decrease the expression of SM-αTM mRNA but did inhibit SM-MHC mRNA expression by 36%. Consistent with the absence of detectable PDGF α-receptors on these cells, PDGF-AA had no effect on either mitogenesis or expression of SM-MHC or SM-αTM. These findings indicate that proliferation, per se, does not coordinately reduce SM-specific protein expression and suggest that circulating or locally produced PDGF-BB may play a generalized role in the modulation of the SMC phenotype to a less differentiated state, a characteristic of SMCs in atherosclerotic blood vessels.