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基质金属蛋白酶与冠状动脉疾病。

Matrix metalloproteinases in coronary artery disease.

出版信息

Adv Clin Chem. 2014;64:1-72. doi: 10.1016/b978-0-12-800263-6.00001-x.

Abstract

Matrix metalloproteinases (MMP) are a family of zinc-containing endoproteinases that degrade extracellular matrix (ECM) components. MMP have important roles in the development, physiology and pathology of cardiovascular system. Metalloproteases also play key roles in adverse cardiovascular remodeling, atherosclerotic plaque formation and plaque instability, vascular smooth muscle cell (SMC) migration and restenosis that lead to coronary artery disease (CAD), and progressive heart failure. The study of MMP in developing animal model cardiovascular systems has been helpful in deciphering numerous pathologic conditions in humans. Increased peripheral blood MMP-2 and MMP-9 in acute coronary syndrome (ACS) may be useful as noninvasive tests for detection of plaque vulnerability. MMP function can be modulated by certain pharmacological drugs that can be exploited for treatment of ACS. CAD is a polygenic disease and hundreds of genes contribute toward its predisposition. A large number of sequence variations in MMP genes have been identified. Case-control association studies have highlighted their potential association with CAD and its clinical manifestations. Although results thus far are inconsistent, meta-analysis has demonstrated that MMP-3 Glu45Lys and MMP-9 1562C/T gene polymorphisms were associated with CAD risk.

摘要

基质金属蛋白酶(MMP)是一类含有锌的内肽酶,可降解细胞外基质(ECM)成分。MMP 在心血管系统的发育、生理和病理中具有重要作用。金属蛋白酶还在心血管不良重构、动脉粥样硬化斑块形成和斑块不稳定、血管平滑肌细胞(SMC)迁移和再狭窄导致的冠状动脉疾病(CAD)以及进行性心力衰竭中发挥关键作用。在发育中的动物模型心血管系统中研究 MMP 有助于破译人类的许多病理状况。急性冠状动脉综合征(ACS)患者外周血 MMP-2 和 MMP-9 的增加可能可作为检测斑块脆弱性的无创性检测。MMP 的功能可以通过某些药理学药物来调节,这些药物可用于治疗 ACS。CAD 是一种多基因疾病,有数百个基因对其易感性有贡献。已经确定了 MMP 基因中的大量序列变异。病例对照关联研究强调了它们与 CAD 及其临床表现的潜在关联。尽管迄今为止的结果不一致,但荟萃分析表明 MMP-3 Glu45Lys 和 MMP-9 1562C/T 基因多态性与 CAD 风险相关。

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