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(Circulation. 1997;96:3555-3560.)
© 1997 American Heart Association, Inc.

Articles

Primate Smooth Muscle Cell Migration From Aortic Explants Is Mediated by Endogenous Platelet-Derived Growth Factor and Basic Fibroblast Growth Factor Acting Through Matrix Metalloproteinases 2 and 9

R. D. Kenagy, PhD; C. E. Hart, PhD; W. G. Stetler-Stevenson, MD, PhD; ; A. W. Clowes, MD

From the Department of Surgery, University of Washington (R.D.K., A.W.C.), and Zymogenetics, Inc, Seattle, Wash (C.E.H.), and Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda, Md (W.G.S.-S.).

Correspondence to Richard Kenagy, PhD, University of Washington School of Medicine, Department of Surgery, Box 356410, 1959 NE Pacific St, Seattle, Wash 98195-6410. E-mail rkenagy{at}u.washington.edu

Background Migration of arterial smooth muscle cells (SMCs) is regulated by basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and matrix metalloproteinases (MMPs) in the injured rat carotid artery. We have recently shown that migration of SMCs from baboon aortic explants depends on the activity of MMPs, but the identity of the stimulatory MMPs and the role of bFGF and PDGF in this primate system are not known.

Methods and Results These experiments were designed to determine whether MMP2, MMP9, bFGF, or PDGF plays a role in SMC migration from medial explants of baboon aorta. Explants were cultured in serum-free medium with insulin, transferrin, and ovalbumin. Neutralizing antibodies to MMP2 and antibodies that inhibit activation of proMMP9 decreased SMC migration from the aortic explants. Antibodies to bFGF and to the - and ß-subunits of the PDGF receptor also inhibited migration from the explants. Addition of bFGF and PDGF-BB but not PDGF-AA increased migration. The antibodies to bFGF but not the antibodies to the PDGF receptor subunits decreased the levels of MMP9, whereas all the antibodies decreased activated MMP2.

Conclusions These data demonstrate that SMC migration from primate aortic explants is dependent on endogenous MMP2, MMP9, PDGF, and bFGF. The data also suggest that PDGF-induced (PDGF-BB or possibly PDGF-AB) migration is dependent on MMP2, whereas bFGF-induced migration depends on both MMP2 and MMP9.

Key Words: atherosclerosis • metalloproteinases • muscle, smooth • platelet-derived factors • tissue