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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1467.)
© 2000 American Heart Association, Inc.

Vascular Biology

Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via _vß₃ Integrin

Michelle P. Bendeck; Colleen Irvin; Michael Reidy; Laura Smith; Diane Mulholland; Michael Horton; Cecilia M. Giachelli

From the Terrence Donnelly Research Laboratories (M.P.B., D.M.), Division of Cardiology, St. Michael’s Hospital, and the Departments of Medicine and Laboratory Medicine and Pathobiology (M.P.B., D.M.), University of Toronto, Toronto, Ontario, Canada; the Department of Pathology (C.I., M.R., L.S., C.M.G.), University of Washington, Seattle; and the Bone and Mineral Centre (M.H.), Department of Medicine, Royal Free and University College Medical School, London, UK.

Correspondence to Dr Michelle Bendeck, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, Room 6315, 1 King’s College Circle, Toronto, Ontario, Canada M55 1A8. E-mail bendeckm{at}smh.toronto.on.ca

Abstract—This study tests the hypothesis that _vß₃ integrin receptors play a critical role in smooth muscle cell (SMC) migration after arterial injury and facilitate migration through the upregulation of matrix metalloproteinase (MMP) activity. We showed that ß₃ integrin mRNA was upregulated by SMCs in the balloon-injured rat carotid artery in coincidence with MMP-1 expression and early SMC migration. Treatment with the ß₃ integrin–blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8±30.8 cells/mm² in control rats to 10.29±7.03 cells/mm² in F11-treated rats (P=0.008). By contrast, there was no effect on medial SMC proliferation or on medial SMC number in the carotid artery at 4 days. In vitro, we found that human newborn SMCs produced MMP-1 but that adult SMCs did not. This was possibly due to the fact that newborn SMCs expressed _vß₃ integrin receptors, whereas adult SMCs did not. Stimulation of newborn (_vß₃+) SMCs with osteopontin, a matrix ligand for _vß₃, increased MMP-1 production from 114.4±35.8 ng/mL at 0 nmol/L osteopontin to 232.5±57.5 ng/mL at 100 nmol/L osteopontin. Finally, we showed that stimulation of newborn SMCs with platelet-derived growth factor-BB and osteopontin together increased the SMC production of MMP-9. Thus, our results support the hypothesis that SMC _vß₃ integrin receptors play an important role in regulating migration by stimulating SMC MMP production.

Key Words: smooth muscle cells • matrix metalloproteinases • _vß₃ integrins • migration • arterial injury

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