Circulation Research, Vol 75, 682-691, Copyright © 1994 by American Heart Association

ARTICLES

Different functions of the platelet-derived growth factor-alpha and - beta receptors for the migration and proliferation of cultured baboon smooth muscle cells

N Koyama, CE Hart and AW Clowes
Department of Surgery, University of Washington, Seattle 98195.

Migration of medial smooth muscle cells (SMCs) and their proliferation in the intima contribute to thickening of injured and atherosclerotic vessels. These events have been proposed to be regulated in part by platelet-derived growth factor (PDGF). Two separate PDGF receptors have been identified, PDGF-R alpha and PDGF-R beta. To study the functions of PDGF-R alpha and PDGF-R beta in vascular SMCs, neutralizing monoclonal antibodies (mAbs) specific for each of the two receptors were used. These antibodies allowed us to evaluate the role of each receptor for PDGF-induced proliferation and migration of cultured baboon SMCs. Both PDGF-AA and PDGF-BB stimulated SMC growth, with PDGF- BB being more potent than PDGF-AA. Studies with anti-PDGF-R alpha and anti-PDGF-R beta mAbs revealed that both PDGF receptors promoted the stimulatory signals for proliferation. In contrast, PDGF-BB stimulated SMC migration, whereas PDGF-AA had no stimulatory activity on its own. Additionally, PDGF-AA was able to suppress migration induced by PDGF-BB or fibronectin in modified Boyden's chamber assay. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, only the chemotactic component was inhibited by PDGF-AA. The suppression of SMC migration by PDGF-AA was eliminated by anti-PDGF-R alpha mAb. In addition, PDGF-BB, in the presence of anti-PDGF-R beta, bound only to PDGF-R alpha and caused suppression of SMC migration induced by fibronectin. These results suggest that when activated by ligand binding, both PDGF-R alpha and PDGF-R beta stimulate proliferation. In contrast, only activation of PDGF-R beta stimulates migration, whereas ligand binding to PDGF-R alpha leads to inhibition of cell migration. These observations provide support for the conclusion that PDGF-R alpha and PDGF-R beta may play different roles in SMC function and may be involved in different regulatory mechanisms during vascular remodeling.

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