Smooth muscle cell matrix metalloproteinase production is stimulated via alpha(v)beta(3) integrin

This study tests the hypothesis that alpha(V)beta(3) integrin receptors pla y a critical role in smooth muscle cell (SMC) migration after arterial inju ry and facilitate migration through the upregulation of matrix metalloprote inase (MMP) activity. We showed that beta(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 beta(3) integrin-bl ocking antibody F11 significantly decreased SMC migration into the intima a t 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 carot id artery at 4 days. In vitro, we found that human newborn SMCs produced MM P-1 but that adult SMCs did not. This was possibly due to the fact that new born SMCs expressed alpha(V)beta(3) integrin receptors, whereas adult SMCs did not, Stimulation of newborn (alpha(V)beta(3)+) SMCs with osteopontin, a matrix ligand for alpha(V)beta(3), increased MMP-1 production from 114.4+/ -35.8 ng/lmL at 0 nmol/L osteopontin to 232.5+/-57.5 ng/mL at 100 nmol/L os teopontin, Finally, we showed that stimulation of newborn SMCs with platele t-derived growth factor-BE and osteopontin together increased the SMC produ ction of MMP-9. Thus, our results support the hypothesis that SMC alpha(V)b eta(3) integrin receptors play an important role in regulating migration by stimulating SMC MMP production.