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