SMOOTH-MUSCLE CELLS ISOLATED FROM THE NEOINTIMA AFTER VASCULAR INJURYEXHIBIT ALTERED RESPONSES TO PLATELET-DERIVED GROWTH-FACTOR AND OTHERSTIMULI

A variety of evidence suggests that vascular smooth muscle cells (SMC) exhibit a more immature phenotype when stimulated by injury to replic ate in the adult. One growth characteristic common to immature (embryo nic, fetal, and neonatal) SMC is a markedly reduced responsiveness to platelet-derived growth factor (PDGF) and other mitogenic stimuli. Her e we demonstrate that SMC isolated from the 14-day neointima of experi mentally injured carotid arteries exhibit a similar growth phenotype. The proliferative responses of neointimal cells to the BB homodimer of PDGF, which interacts with both forms of the PDGF receptor, were up t o twenty-fold less (as assessed by BrdU immunocytochemistry) than that of adult control tunica media eel Is over a wide range of PDGF concen trations. Paradoxically, these cells expressed abundant mRNA for the a lpha- and beta-subunits of the PDGF receptor (by RT-PCR) and expressed abundant PDGF receptor protein (by Western blotting). Addition of PDG F-BB to neointimal SMC induced significant autophosphorylation of the PDGF receptor, suggesting that the PDGF receptors were fully functiona l. The chemotactic responses of neointimal SMC to PDGF, in in vitro mi gration assays, were identical to that of control medial cells. The da ta further establish the existence of vascular SMC phenotypes characte rized by a refractoriness to growth stimulation by specific mitogens, and provide further evidence for the reiteration of developmentally re gulated programs following vascular injury in vivo. (C) 1996 Wiley-Lis s, Inc.