HMG-CoA reductase inhibitors reduce matrix metalloproteinase-9 activity in human varicose veins
HMG-CoA reductase inhibitors reduce matrix metalloproteinase-9 activity in human varicose veins
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DOI：
10.1159/000090339
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发表时间：
2005-01-01
影响因子：
1.6
通讯作者：
Hamano, K
中科院分区：
文献类型：
--
作者：
Nomura, S;Yoshimura, K;Hamano, K
基质金属蛋白酶（MMPs）与静脉曲张的组织降解有关。本研究的目的是探讨3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）对曲张静脉基质金属蛋白酶活性的影响。MMP-9在曲张静脉中的水平显著高于对照组，并且主要定位于图尼卡中膜的平滑肌细胞中，在此处观察到细胞外基质的显著降解。辛伐他汀和普伐他汀显着抑制MMP-9活性在离体培养的静脉曲张。辛伐他汀在mRNA和蛋白水平以及尿激酶型纤溶酶原激活物蛋白水平抑制MMP-9，导致肿瘤坏死因子-α诱导的MMP-9活性的显著抑制。因此，他汀类药物通过多种机制抑制静脉曲张中MMP-9的活性，表明它们可能具有治疗这种疾病的临床潜力。版权所有（C）2005 S. Karger AG，巴塞尔。
Matrix metalloproteinases (MMPs) have been implicated in tissue degradation in varicose veins. The aim of this study was to investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on the activity of MMPs in varicose veins. MMP-9 was present at significantly higher levels in varicose veins than in controls and was localized mainly in smooth muscle cells at the tunica media, where marked degradation of the extracellular matrix was observed. Both simvastatin and pravastatin strikingly suppressed MMP-9 activity in ex vivo culture of varicose veins. Simvastatin suppressed MMP-9 at both the mRNA and protein levels as well as at the urokinase-type plasminogen activator protein level, resulting in the dramatic suppression of MMP-9 activity induced by tumor necrosis factor-alpha. Therefore, statins suppress MMP-9 activity by multiple mechanisms in varicose veins, suggesting they may have clinical potential for the treatment of this disease. Copyright (C) 2005 S. Karger AG, Basel.