Regulation and involvement of matrix metalloproteinases in vascular diseases.
Regulation and involvement of matrix metalloproteinases in vascular diseases.
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DOI：
10.2741/4378
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Sen U
中科院分区：
文献类型：
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作者：
Amin M;Pushpakumar S;Muradashvili N;Kundu S;Tyagi SC;Sen U
基质金属蛋白酶（matrix metalloproteinases，MMPs）是一类锌依赖性内肽酶，其主要功能是降解和存款细胞外基质（extracellular matrix，ECM）中的结构蛋白。MMPs的失调与血管疾病有关。MMPs分为胶原酶、明胶酶、膜型、金属弹性蛋白酶、基质溶素、基质溶素、釉质溶素和未分类的亚类。MMPs的产生受到氧化应激、生长因子和炎症等因素的刺激，导致其上调或下调，随后ECM重塑。正常情况下，MMPs的过度激活受其内源性抑制剂，金属蛋白酶组织抑制剂（TIMPs）的控制。MMPs和TIMPs的失衡与高血压、动脉粥样硬化斑块形成和不稳定、主动脉瘤和静脉曲张壁重塑有关。此外，最近的证据表明，表观遗传调节的一些基质金属蛋白酶在血管生成和动脉粥样硬化。多年来，MMPs的药理学抑制剂已被用于改变或预防疾病的发展，并取得了一些成功。在这篇综述中，我们讨论了MMP生物学的最新进展，及其参与血管疾病的表现。
Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases whose main function is to degrade and deposit structural proteins within the extracellular matrix (ECM). A dysregulation of MMPs is linked to vascular diseases. MMPs are classified into collagenases, gelatinases, membrane-type, metalloelastase, stromelysins, matrilysins, enamelysins, and unclassified subgroups. The production of MMPs is stimulated by factors such as oxidative stress, growth factors and inflammation which lead to its up- or down-regulation with subsequent ECM remodeling. Normally, excess activation of MMPs is controlled by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). An imbalance of MMPs and TIMPs has been implicated in hypertension, atherosclerotic plaque formation and instability, aortic aneurysms and varicose vein wall remodeling. Also, recent evidence suggests epigenetic regulation of some MMPs in angiogenesis and atherosclerosis. Over the years, pharmacological inhibitors of MMPs have been used to modify or prevent the development of the disease with some success. In this review, we discuss recent advances in MMP biology, and their involvement in the manifestation of vascular disease.