Institute of Cardiovascular Sciences, St Boniface Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Int J Cardiol. 2013 Mar 20;164(1):39-47. doi: 10.1016/j.ijcard.2012.01.103. Epub 2012 Feb 20.
Various procedures such as angioplasty, thrombolytic therapy, coronary bypass surgery, and cardiac transplantation are invariably associated with ischemia-reperfusion (I/R) injury. Impaired recovery of cardiac function due to I/R injury is considered to be a consequence of the occurrence of both oxidative stress and intracellular Ca(2+)-overload in the myocardium. These changes in the ischemic myocardium appear to activate both extracellular and intracellular proteases which are responsible for the cleavage of extracellular matrix and subcellular structures involved in the maintenance of cardiac function. It is thus intended to discuss the actions of I/R injury on several proteases, with a focus on calpain, matrix metalloproteinases, and cathepsins as well as their role in inducing alterations both inside and outside the cardiomyocytes. In addition, modifications of subcellular organelles such as myofibrils, sarcoplasmic reticulum and sarcolemma as well as extracellular matrix, and the potential regulatory effects of endogenous inhibitors on protease activities are identified. Both extracellular and intracellular proteolytic activities appear to be imperative in determining the true extent of I/R injury and their inhibition seems to be of critical importance for improving the recovery of cardiac function. Thus, both extracellular and intracellular proteases may serve as potential targets for the development of cardioprotective interventions for reducing damage to the heart and retarding the development of contractile dysfunction caused by I/R injury.
各种程序，如血管成形术、溶栓治疗、冠状动脉旁路手术和心脏移植，都不可避免地与缺血再灌注（I/R）损伤有关。由于 I/R 损伤导致的心脏功能恢复受损被认为是心肌中氧化应激和细胞内 Ca(2+)-超载同时发生的结果。缺血心肌中的这些变化似乎激活了细胞外和细胞内的蛋白酶，这些蛋白酶负责切割细胞外基质和参与维持心脏功能的亚细胞结构。因此，本文旨在讨论 I/R 损伤对几种蛋白酶的作用，重点讨论钙蛋白酶、基质金属蛋白酶和组织蛋白酶，以及它们在诱导心肌细胞内外变化中的作用。此外，还确定了亚细胞器（如肌原纤维、肌浆网和肌膜）以及细胞外基质的改变，以及内源性抑制剂对蛋白酶活性的潜在调节作用。细胞外和细胞内的蛋白水解活性似乎对确定 I/R 损伤的真实程度至关重要，抑制它们对于改善心脏功能的恢复似乎至关重要。因此，细胞外和细胞内的蛋白酶都可以作为开发心脏保护干预措施的潜在靶点，以减少心脏损伤并延缓由 I/R 损伤引起的收缩功能障碍的发展。
