Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Side Hamburg/Kiel/Lübeck, Hamburg, Germany.
Basic Res Cardiol. 2023 May 9;118(1):18. doi: 10.1007/s00395-023-00987-2.
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Most cardiovascular deaths are caused by ischaemic heart diseases such as myocardial infarction (MI). Hereby atherosclerosis in the coronary arteries often precedes disease manifestation. Since tissue remodelling plays an important role in the development and progression of atherosclerosis as well as in outcome after MI, regulation of matrix metalloproteinases (MMPs) as the major ECM-degrading enzymes with diverse other functions is crucial. Here, we provide an overview of the expression profiles of MMPs in coronary artery and left ventricular tissue using publicly available data from whole tissue to single-cell resolution. To approach an association between MMP expression and the development and outcome of CVDs, we further review studies investigating polymorphisms in MMP genes since polymorphisms are known to have an impact on gene expression. This review therefore aims to shed light on the role of MMPs in atherosclerosis and MI by summarizing current knowledge from publically available datasets, human studies, and analyses of polymorphisms up to preclinical and clinical trials of pharmacological MMP inhibition.
心血管疾病(CVDs)仍然是全球死亡的主要原因。大多数心血管死亡是由缺血性心脏病引起的,如心肌梗死(MI)。在此,冠状动脉中的动脉粥样硬化通常先于疾病表现。由于组织重塑在动脉粥样硬化的发展和进展以及 MI 后的结果中起着重要作用,因此调节基质金属蛋白酶(MMPs)作为主要的 ECM 降解酶以及具有多种其他功能的酶至关重要。在这里,我们使用来自整个组织到单细胞分辨率的公开可用数据,概述了 MMPs 在冠状动脉和左心室组织中的表达谱。为了探讨 MMP 表达与 CVD 发展和结果之间的关系,我们进一步综述了研究 MMP 基因多态性的研究,因为多态性已知会影响基因表达。因此,本综述旨在通过总结来自公开数据集、人类研究以及对多态性的分析的现有知识,阐明 MMPs 在动脉粥样硬化和 MI 中的作用,这些分析的范围包括药理学 MMP 抑制的临床前和临床试验。