Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability.
Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability.
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DOI：
10.1159/000446703
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发表时间：
2016
影响因子：
1.7
通讯作者：
Jones JA
中科院分区：
文献类型：
--
作者：
Ruddy JM;Ikonomidis JS;Jones JA
动脉粥样硬化性疾病的患病率持续增加，尽管目前的医疗干预措施显著降低了主要心血管事件，但仍存在额外的治疗窗口。动脉粥样硬化斑块生长是胆固醇渗透、炎性细胞浸润、血管平滑肌细胞（VSMC）迁移和新生血管侵袭的复杂整合。基质金属蛋白酶（MMP）是基质降解蛋白酶家族，参与血管重塑的各个阶段。在动脉粥样硬化病变的发生和发展中，特异性基质金属蛋白酶对内皮细胞完整性和VSMC迁移的贡献已通过这些蛋白酶在血浆和斑块标本中的表达增加得到证实。基质金属蛋白酶组织抑制剂（TIMPs）的内源性阻断可能会减弱某些区域的蛋白水解，但基质变性的进展表明，基质金属蛋白酶占主导地位的动脉粥样硬化斑块，沉淀脆弱性。斑块新血管形成也有助于不稳定性，并且将MMP在血管生成中的已知作用与动脉粥样硬化斑块生长的已知作用相结合，靶向MMP以促进斑块稳定的兴趣继续积累。本文旨在综述MMPs和TIMPs对动脉粥样硬化斑块扩张、新生血管形成和破裂脆弱性的作用，以期促进靶向治疗，改善斑块稳定性，降低主要心血管事件的风险。
The prevalence of atherosclerotic disease continues to increase, and despite significant reductions in major cardiovascular events with current medical interventions, an additional therapeutic window exists. Atherosclerotic plaque growth is a complex integration of cholesterol penetration, inflammatory cell infiltration, vascular smooth muscle cell (VSMC) migration, and neovascular invasion. A family of matrix-degrading proteases, the matrix metalloproteinases (MMPs), contributes to all phases of vascular remodeling. The contribution of specific MMPs to endothelial cell integrity and VSMC migration in atherosclerotic lesion initiation and progression has been confirmed by the increased expression of these proteases in plasma and plaque specimens. Endogenous blockade of MMPs by the tissue inhibitors of metalloproteinases (TIMPs) may attenuate proteolysis in some regions, but the progression of matrix degeneration suggests that MMPs predominate in atherosclerotic plaque, precipitating vulnerability. Plaque neovascularization also contributes to instability and, coupling the known role of MMPs in angiogenesis to that of atherosclerotic plaque growth, interest in targeting MMPs to facilitate plaque stabilization continues to accumulate. This article aims to review the contributions of MMPs and TIMPs to atherosclerotic plaque expansion, neovascularization, and rupture vulnerability with an interest in promoting targeted therapies to improve plaque stabilization and decrease the risk of major cardiovascular events.
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影响因子：
3.7
作者：
Abbas A;Aukrust P;Russell D;Krohg-Sørensen K;Almås T;Bundgaard D;Bjerkeli V;Sagen EL;Michelsen AE;Dahl TB;Holm S;Ueland T;Skjelland M;Halvorsen B
通讯作者：
Halvorsen B
DOI：
10.1161/01.atv.0000121571.78696.dc
发表时间：
2004-04-01
影响因子：
8.7
作者：
Brown, DL;Desai, KK;Golub, LM
通讯作者：
Golub, LM
影响因子：
10.8
作者：
Bond, M;Chase, AJ;Newby, AC
通讯作者：
Newby, AC
DOI：
10.1161/atvbaha.111.238402
发表时间：
2012-01-01
影响因子：
8.7
作者：
Casagrande, Viviana;Menghini, Rossella;Federici, Massimo
通讯作者：
Federici, Massimo
影响因子：
10.8
作者：
Aguilera, CM;George, SJ;Newby, AC
通讯作者：
Newby, AC