Jenkins G M, Crow M T, Bilato C, Gluzband Y, Ryu W S, Li Z, Stetler-Stevenson W, Nater C, Froehlich J P, Lakatta E G, Cheng L
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Md 21224, USA.
Circulation. 1998;97(1):82-90. doi: 10.1161/01.cir.97.1.82.
Remodeling of the injured vascular wall is dependent on the action of several extracellular proteases. Previous studies have shown that expression of matrix metalloproteinases (MMP-2 and MMP-9) is upregulated after vascular injury and that MMP-2 is required for the migration of cultured vascular smooth muscle cells across complex extracellular matrix barriers. The present study examined changes in the expression of membrane-type metalloproteinase (MT-MMP-1), a putative regulator of MMP-2, in the tissue localization of MMP-2, and in the expression of activated and latent forms of MMP-2 and the tissue inhibitor of metalloproteinases, TIMP-2, in rat carotid arteries subjected to balloon catheter injury.
MT-MMP-1 mRNA levels increased sixfold after 3 days of injury, coinciding with an increase in MMP-2 activation assessed by gelatin zymography. Western blotting and gelatin zymography showed an increase in MMP-2 protein levels beginning 5 to 7 days after injury; immunocytochemistry and Western blotting showed that the increase occurred preferentially in the developing neointima.
These results show that increased expression of MT-MMP-1 and activation of MMP-2 occurs early after injury to the rat carotid artery and that at later times MMP-2 is preferentially localized to the developing neointima.
受损血管壁的重塑依赖于多种细胞外蛋白酶的作用。先前的研究表明，血管损伤后基质金属蛋白酶（MMP - 2和MMP - 9）的表达上调，并且MMP - 2是培养的血管平滑肌细胞穿越复杂细胞外基质屏障所必需的。本研究检测了膜型金属蛋白酶（MT - MMP - 1）（一种假定的MMP - 2调节因子）的表达变化、MMP - 2在组织中的定位，以及在接受球囊导管损伤的大鼠颈动脉中MMP - 2激活形式和潜伏形式的表达以及金属蛋白酶组织抑制剂TIMP - 2的表达。
损伤3天后，MT - MMP - 1 mRNA水平增加了6倍，这与通过明胶酶谱法评估的MMP - 2激活增加相一致。蛋白质印迹法和明胶酶谱法显示，损伤后5至7天开始MMP - 2蛋白水平增加；免疫细胞化学和蛋白质印迹法显示，这种增加优先发生在正在形成的新生内膜中。
这些结果表明，大鼠颈动脉损伤后早期MT - MMP - 1表达增加和MMP - 2激活，并且在后期MMP - 2优先定位于正在形成的新生内膜。
