Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Center for Heart and Vascular Research, Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska.
Am J Physiol Heart Circ Physiol. 2020 Mar 1;318(3):H706-H714. doi: 10.1152/ajpheart.00679.2019. Epub 2020 Feb 21.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that break down extracellular matrix (ECM) components and have shown to be highly active in the myocardial infarction (MI) landscape. In addition to breaking down ECM products, MMPs modulate cytokine signaling and mediate leukocyte cell physiology. MMP-2, -7, -8, -9, -12, -14, and -28 are well studied as effectors of cardiac remodeling after MI. Whereas 13 MMPs have been evaluated in the MI setting, 13 MMPs have not been investigated during cardiac remodeling. Here, we measure the remaining MMPs across the MI time continuum to provide the full catalog of MMP expression in the left ventricle after MI in mice. We found that MMP-10, -11, -16, -24, -25, and -27 increase after MI, whereas MMP-15, -17, -19, -21, -23b, and -26 did not change with MI. For the MMPs increased with MI, the macrophage was the predominant cell source. This work provides targets for investigation to understand the full complement of specific MMP roles in cardiac remodeling. To date, a number of matrix metalloproteinases (MMPs) have not been evaluated in the left ventricle after myocardial infarction (MI). This article supplies the missing knowledge to provide a complete MI MMP compendium.
基质金属蛋白酶(MMPs)是一类能分解细胞外基质(ECM)成分的蛋白水解酶,在心肌梗死(MI)中表现出高度活性。除了分解 ECM 产物外,MMPs 还调节细胞因子信号转导并介导白细胞细胞生理学。MMP-2、-7、-8、-9、-12、-14 和 -28 已被广泛研究为 MI 后心脏重构的效应物。尽管已有 13 种 MMP 在 MI 背景下得到了评估,但在心脏重构期间尚未研究过其余的 13 种 MMP。在这里,我们在 MI 的时间连续体上测量了剩余的 MMP,以提供 MI 后小鼠左心室中 MMP 表达的完整目录。我们发现 MMP-10、-11、-16、-24、-25 和 -27 在 MI 后增加,而 MMP-15、-17、-19、-21、-23b 和 -26 与 MI 无关。对于与 MI 增加的 MMP,巨噬细胞是主要的细胞来源。这项工作为研究提供了目标,以了解心脏重构中特定 MMP 作用的完整作用。迄今为止,在心肌梗死后,尚未在左心室中评估许多基质金属蛋白酶(MMPs)。本文提供了缺失的知识,以提供完整的 MI MMP 纲要。