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整合素金属蛋白酶:血管生成、炎症和动脉粥样硬化中的分子剪刀。

A disintegrin and metalloproteases: molecular scissors in angiogenesis, inflammation and atherosclerosis.

机构信息

Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

出版信息

Atherosclerosis. 2012 Oct;224(2):302-8. doi: 10.1016/j.atherosclerosis.2012.04.023. Epub 2012 May 8.

Abstract

A disintegrin and metalloproteases (ADAMs) are enzymes that cleave (shed) the extracellular domains of various cell surface molecules, e.g. adhesion molecules, cytokine/chemokine and growth factor receptors, thereby releasing soluble molecules that can exert agonistic or antagonistic functions or serve as biomarkers. By functioning as such molecular scissors, ADAM proteases have been implicated in various diseases, e.g. cancer, and their role in cardiovascular diseases is now emerging. This review will focus on the role of ADAM proteases in molecular mechanisms of angiogenesis and inflammation in relation to atherosclerosis. Besides a concise overview of the current state and recent advances of this research area, we will discuss key questions about redundancy, specificity and regulation of ADAM proteases and emphasize the importance of confirmation of in vitro findings in in vivo models.

摘要

解整合素金属蛋白酶(ADAMs)是一类能够切割(脱落)多种细胞表面分子胞外结构域的酶,例如黏附分子、细胞因子/趋化因子和生长因子受体,从而释放出具有激动或拮抗功能的可溶性分子,或者作为生物标志物。ADAM 蛋白酶作为这样的分子剪刀,与各种疾病有关,例如癌症,其在心血管疾病中的作用也正在显现。这篇综述将重点介绍 ADAM 蛋白酶在与动脉粥样硬化相关的血管生成和炎症的分子机制中的作用。除了简要概述这一研究领域的现状和最新进展外,我们还将讨论 ADAM 蛋白酶的冗余性、特异性和调控的关键问题,并强调在体内模型中验证体外发现的重要性。

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