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Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor
R D Kenagy1, C E Hart, W G Stetler-Stevenson
1Department of Surgery, University of Washington, Seattle 98195-6410, USA. rkenagy@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 alpha- and beta-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.
Insights
Smooth muscle cell migration in primates depends on matrix metalloproteinases (MMPs), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). These factors are crucial for understanding arterial repair mechanisms.
Area of Science:
- Vascular Biology
- Cellular Signaling
- Extracellular Matrix
Background:
- Smooth muscle cell (SMC) migration is vital in vascular repair, influenced by growth factors and matrix metalloproteinases (MMPs).
- Previous studies in rats identified basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and MMPs in regulating SMC migration.
- The specific roles of these factors and MMPs in primate SMC migration remain uncharacterized.
Purpose of the Study:
- To investigate the roles of MMP2, MMP9, bFGF, and PDGF in SMC migration from baboon aortic explants.
- To elucidate the signaling pathways involved in primate SMC migration.
Main Methods:
- Baboon aortic explants were cultured in serum-free medium.
- Neutralizing antibodies against MMP2, bFGF, and PDGF receptor subunits were used.
- Antibodies inhibiting proMMP9 activation were employed.
- Recombinant PDGF-BB, PDGF-AA, and bFGF were added to assess their effects on migration.
Main Results:
- Antibodies against MMP2 and proMMP9 activation significantly reduced SMC migration.
- Antibodies targeting bFGF and PDGF receptors also inhibited migration.
- bFGF and PDGF-BB, but not PDGF-AA, enhanced SMC migration.
- bFGF-induced migration involved both MMP2 and MMP9, while PDGF-BB-induced migration primarily depended on MMP2.
Conclusions:
- SMC migration from primate aortic explants is dependent on endogenous MMP2, MMP9, PDGF, and bFGF.
- PDGF-induced migration relies on MMP2, whereas bFGF-induced migration requires both MMP2 and MMP9.
- These findings highlight the complex interplay of growth factors and MMPs in primate vascular SMC migration.