Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via α v β 3 Integrin

Author:

Bendeck Michelle P.1,Irvin Colleen1,Reidy Michael1,Smith Laura1,Mulholland Diane1,Horton Michael1,Giachelli Cecilia M.1

Affiliation:

1. 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.

Abstract

Abstract —This study tests the hypothesis that α v β 3 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 β 3 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 β 3 integrin–blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8±30.8 cells/mm 2 in control rats to 10.29±7.03 cells/mm 2 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 α v β 3 integrin receptors, whereas adult SMCs did not. Stimulation of newborn (α v β 3 +) SMCs with osteopontin, a matrix ligand for α v β 3 , 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 α v β 3 integrin receptors play an important role in regulating migration by stimulating SMC MMP production.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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