Serum starvation and growth factor receptor expression in vascular smooth muscle cells

Background: Smooth muscle cell (SMC) proliferation in atherosclerosis is regulated through the interaction of growth factors like platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) and their receptors ( R). We hypothesized that serum starvation of SMCs may affect PDGF beta-R and IGF-1-R expression and, consequently, the effect of their cognate ligands on SMC survival/proliferation. Methods and Results: Serum starvation significantly increases PDGF beta-R but not IGF-1-R mRNA and protein expression in SMCs. PDGF- BB stimulates cell survival but not proliferation in serum-starved SMCs of the synthetic phenotype, whereas SMCs of the contractile phenotype respond to PDGF- BB by a significant increase in proliferation. Immunohistochemical analysis of coronary atherosclerotic lesions reveals PDGF beta-R expression in SMCs in the lamina fibromuscularis, but not in the media and in healthy parts of the arterial wall. No such differential expression was observed for IGF-1-R. Conclusions: Differential regulation of PDGF beta-R and IGF-1-R expression by serum starvation might represent a mechanism for the control of SMC survival/proliferation in atherogenesis and restenosis. The distribution of PDGF beta-Rs and IGF-1-Rs in atherosclerotic lesions may indicate an effect of serum starvation on SMCs in the arterial wall. Copyright (C) 2006 S. Karger AG, Basel.