Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
Trends Cardiovasc Med. 2011 May;21(4):112-8. doi: 10.1016/j.tcm.2012.03.008.
Matrix metalloproteinases (MMPs) have been almost exclusively thought to be secreted proteases (with the exception of the membrane-type MMPs) that exert diverse biological actions in health and disease via proteolyzing substrates outside the cell. However, recent evidence has demonstrated that the role of MMPs goes far beyond their proteolytic activity in the extracellular matrix. MMP-2 is arguably the most ubiquitous member of the 23 member MMP family and is expressed in all cells of the heart and vasculature. In the past 10 years, MMP-2 was shown to change the bioactivity of a growing list of specific, non-extracellular matrix proteins both outside and inside the cell. There is clear evidence of its intracellular localization to the cardiac sarcomere, nucleus, and mitochondria and that during early phases of oxidative stress injury to the heart, MMP-2 proteolyzes specific sarcomeric and cytoskeletal proteins to cause contractile dysfunction. In this review we discuss this novel intracellular biology of MMP-2 and the potential use of MMP inhibitors for the therapy of heart injury caused by oxidative stress.
基质金属蛋白酶（MMPs）几乎被认为是分泌型蛋白酶（膜型 MMPs 除外），它们通过细胞外的基质蛋白水解作用在健康和疾病中发挥多种生物学作用。然而，最近的证据表明，MMPs 的作用远不止于其在细胞外基质中的蛋白水解活性。MMP-2 可以说是 23 种 MMP 家族成员中最普遍的成员，存在于心脏和血管的所有细胞中。在过去的 10 年中，MMP-2 被证明可以改变越来越多特定的、非细胞外基质蛋白的生物活性，这些蛋白既存在于细胞外，也存在于细胞内。有明确的证据表明，它在心脏肌节、细胞核和线粒体中的细胞内定位，并且在心脏氧化应激损伤的早期阶段，MMP-2 对特定的肌节和细胞骨架蛋白进行蛋白水解，导致收缩功能障碍。在这篇综述中，我们讨论了 MMP-2 的这种新的细胞内生物学特性，以及 MMP 抑制剂在治疗氧化应激引起的心脏损伤方面的潜在用途。
