Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via avb3 Integrin
نویسندگان
چکیده
This study tests the hypothesis that avb3 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 b3 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 b3 integrin–blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8630.8 cells/mm in control rats to 10.2967.03 cells/mm in F11-treated rats (P50.008). 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 avb3 integrin receptors, whereas adult SMCs did not. Stimulation of newborn (avb31) SMCs with osteopontin, a matrix ligand for avb3, increased MMP-1 production from 114.4635.8 ng/mL at 0 nmol/L osteopontin to 232.5657.5 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 avb3 integrin receptors play an important role in regulating migration by stimulating SMC MMP production. (Arterioscler Thromb Vasc Biol. 2000;20:1467-1472.)
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تاریخ انتشار 2000