Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling.

Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling.
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DOI:
10.1038/s41569-018-0022-z
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发表时间:
2018-08
期刊:
Nature reviews. Cardiology
影响因子:
--
通讯作者:
Lindsey ML
Lindsey ML
中科院分区:
其他
文献类型:
--
作者:
Lindsey ML

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基质金属蛋白酶(MMPs)及其内源性抑制物在心肌中的研究已有20年的历史。不完整的知识库和抑制剂的实验设计问题阻碍了翻译的尝试,但临床兴趣仍然很高,因为MMPs与心肌梗死(MI)后的结果之间存在强烈的关联,以及机制研究表明MMPs参与了MI伤口愈合过程的多个阶段。本文重点介绍了我们对基质金属蛋白酶的理解是如何从一维的早期关注于测量基质金属蛋白酶的活性、监测基质金属蛋白酶与抑制物的比例以及评价一种基质金属蛋白酶-底物对,发展到目前使用系统生物学方法来整合整个基质金属蛋白酶在心肌梗死后的反应中的作用。以MMP9为例,解释这些概念,并为研究MMPs作为心脏重塑的机械性介质提供一个模板。
Matrix metalloproteinases (MMPs) and their endogenous inhibitors have been studied in the myocardium for the past 2 decades. An incomplete knowledge base and experimental design issues with inhibitors have hampered attempts at translation, but clinical interest remains high because of strong associations between MMPs and outcomes after myocardial infarction (MI) as well as mechanistic studies showing MMP involvement at multiple stages of the MI wound-healing process. This Review focuses on how our understanding of MMPs has evolved from a one-dimensional early focus on measuring MMP activity, monitoring MMP:inhibitor ratios, and evaluating one MMP–substrate pair to the current use of systems biology approaches to integrate the whole MMP repertoire of roles in the left ventricular response to MI. MMP9 is used as an example MMP to explain these concepts and to provide a template for examining MMPs as mechanistic mediators of cardiac remodelling.
心肌梗塞和心力衰竭中的基质金属蛋白酶。
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