© 2000 American Heart Association, Inc.
Vascular Biology |
Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via 
vß3 Integrin
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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