Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease.
Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease.
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DOI：
10.1016/bs.apha.2017.08.002
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Khalil RA
中科院分区：
文献类型：
--
作者：
Wang X;Khalil RA
基质金属蛋白酶 (MMP) 是锌依赖性内肽酶家族，可降解细胞外基质 (ECM) 中的各种蛋白质。通常，MMP 具有前肽序列、具有催化锌的催化金属蛋白酶结构域、铰链区或连接肽以及血红素结合蛋白结构域。 MMP 通常根据其底物及其结构域的组织分为胶原酶、明胶酶、基质溶解素、基质溶解素、膜型 (MT)-MMP 和其他 MMP。 MMP 由许多细胞分泌，包括成纤维细胞、血管平滑肌 (VSM) 和白细胞。 MMP 在 mRNA 表达水平上受到调节，并通过从其潜在酶原形式中去除前肽结构域来激活。 MMP 通常以无活性的 proMMP 形式分泌，该形式可被包括其他 MMP 在内的各种蛋白酶裂解为活性形式。 MMP 降解 ECM 中的各种蛋白质底物，包括胶原蛋白和弹性蛋白。 MMP 还可以影响内皮细胞功能以及 VSM 细胞迁移、增殖、Ca2+ 信号传导和收缩。 MMP 在血管生成、胚胎发生、形态发生和伤口修复等各种生物过程中的血管组织重塑中发挥作用。特定MMP的改变可影响动脉重塑并导致各种病理性疾病，如高血压、先兆子痫、动脉粥样硬化、动脉瘤形成以及静脉过度扩张和下肢静脉疾病。 MMP 通常受到内源性金属蛋白酶组织抑制剂 (TIMP) 的调节，MMP/TIMP 比率通常决定 ECM 蛋白降解和组织重塑的程度。 MMP 可作为某些血管疾病的生物标志物和潜在治疗靶点。
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM) and leukocytes. MMPs are regulated at the level of mRNA expression and by activation through removal of the propeptide domain from their latent zymogen form. MMPs are often secreted in an inactive proMMP form which is cleaved to the active form by various proteinases including other MMPs. MMPs degrade various protein substrates in ECM including collagen and elastin. MMPs could also influence endothelial cell function as well as VSM cell migration, proliferation, Ca2+ signaling and contraction. MMPs play a role in vascular tissue remodeling during various biological processes such as angiogenesis, embryogenesis, morphogenesis and wound repair. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension, preeclampsia, atherosclerosis, aneurysm formation, as well as excessive venous dilation and lower extremity venous disease. MMPs are often regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs may serve as biomarkers and potential therapeutic targets for certain vascular disorders.