Ischemic heart disease remains a leading cause of human mortality worldwide. One form of ischemic heart disease is ischemia–reperfusion injury caused by the reintroduction of blood supply to ischemic cardiac muscle. The short and long-term damage that occurs due to ischemia–reperfusion injury is partly due to the proteolysis of diverse protein substrates inside and outside of cardiomyocytes. Ischemia–reperfusion activates several diverse intracellular proteases, including, but not limited to, matrix metalloproteinases, calpains, cathepsins, and caspases. This review will focus on the biological roles, intracellular localization, proteolytic targets, and inhibitors of these proteases in cardiomyocytes following ischemia–reperfusion injury. Recognition of the intracellular function of each of these proteases includes defining their activation, proteolytic targets, and their inhibitors during myocardial ischemia–reperfusion injury. This review is a step toward a better understanding of protease activation and involvement in ischemic heart disease and developing new therapeutic strategies for its treatment.

缺血性心脏病仍然是全世界人类死亡的主要原因。缺血性心脏病的一种形式是由重新引入缺血心肌的血液供应引起的缺血再灌注损伤。缺血再灌注损伤造成的短期和长期损伤部分是由于心肌细胞内外多种蛋白质底物的蛋白水解所致。缺血再灌注会激活多种不同的细胞内蛋白酶，包括但不限于基质金属蛋白酶、钙蛋白酶、组织蛋白酶和半胱天冬酶。本综述将重点关注缺血再灌注损伤后心肌细胞中这些蛋白酶的生物学作用、细胞内定位、蛋白水解靶点和抑制剂。对每种蛋白酶的细胞内功能的识别包括定义它们在心肌缺血再灌注损伤期间的激活、蛋白水解靶标及其抑制剂。本综述是朝着更好地了解蛋白酶激活和参与缺血性心脏病并为其治疗制定新的治疗策略迈出的一步。