Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury
Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury
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DOI：
10.1161/01.res.0000040420.17366.2e
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发表时间：
2002-11-01
影响因子：
20.1
通讯作者：
Reidy, MA
中科院分区：
文献类型：
--
作者：
Cho, A;Reidy, MA
基质金属蛋白酶（MMP），特别是MMP-9对于平滑肌细胞（SMC）迁移到内膜中是重要的。在这项研究中，我们试图确定是否MMP-9是至关重要的SMC迁移和形成的新生内膜，通过使用小鼠中的基因被删除（MMP-9（-/-）小鼠）。野生型小鼠动脉的裸露损伤促进了。6天时，中膜SMC迁移到新生内膜中，28天后观察到大的新生内膜损伤。在野生型动脉中，中膜SMC复制在第4天约为8%，第6天为6%，第8天为4%，第14天进一步下降至1%。损伤后第8天内膜细胞复制率为65%，第14天下降到10%左右。在MMP-9（-/-）动脉中，SMC复制在第8天显著降低。此外，SMC迁移和动脉病变生长在MMP-9（-/-）动脉显着受损。从MMP-9（-/-）小鼠动脉中分离的SMCs在体外表现出迁移和复制的损伤。因此，我们目前的数据表明，MMP-9是至关重要的动脉病变的发展，通过调节SMC迁移和增殖。
Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9(-/-) mice). A denuding injury to the arteries of wild-type mice promoted the. migration of medial SMCs into the neointima at 6 days, and a large neointimal lesion was observed after 28 days. In wild-type arteries, medial SMC replication was approximate to8% at day 4, 6% at day 6, and 4% at day 8 and had further decreased to 1% at day 14. Intimal cell replication was 65% at 8 days and had decreased to approximate to10% at 14 days after injury. In MMP-9(-/-) arteries, SMC replication was significantly lower at day 8. In addition, SMC migration and arterial lesion growth were significantly impaired in MMP-9(-/-) arteries. SMCs, isolated from MMP-9(-/-) mouse arteries, showed an impairment of migration and replication in vitro. Thus, our present data indicate that MMP-9 is critical for the development of arterial lesions by regulating both SMC migration and proliferation.