Inhibition of GPR35 Preserves Mitochondrial Function After Myocardial Infarction by Targeting Calpain 1/2. Issue 6 (June 2020)

• Record Type: Journal Article
• Authors: Chen, Ken; He, Lei; Li, Yong; Li, Xiuchuan; Qiu, Chenming; Pei, Haifeng; Yang, Dachun
• Is Part Of: Journal of cardiovascular pharmacology. Volume 75:Issue 6(2020)
• Publication Date: 2020-06
• Subjects: myocardial infarction -- GPR35 -- calpain -- mitochondria; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000819
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Abstract: Ischemia and anoxia-induced mitochondrial impairment may be a key factor leading to heart injury during myocardial infarction (MI). Calpain 1 and 2 are involved in the MI-induced mitochondria injury. G protein-coupled receptor 35 (GPR35) could be triggered by hypoxia. Whether or not GPR35 regulates calpain 1/2 in the pathogenesis of MI is still unclear. In this study, we determined that MI increases GPR35 expression in myocardial tissue. Suppression of GPR35 protects heart from MI injury in mice through reduction of reactive oxygen species activity and mitochondria-dependent apoptosis. Further studies show that GPR35 regulates calpain 1/2. Suppression of GPR35 reduces the expression and activity of calpain 1/2, and alleviates calpain 1/2-associated mitochondrial injury to preserve cardiac function. Based on these data, we conclude that a functional inhibition of GPR35 downregulates calpain 1/2 and contributes to maintenance of cardiac function under pathologic conditions with mitochondrial disorder. In conclusion, our study showed that the identified regulation by GPR35 of calpain 1/2 has important implications for the pathogenesis of MI. Targeting the action of GPR35 and calpain 1/2 in mitochondria presents a potential therapeutic intervention for MI. Abstract : Supplemental Digital Content is Available in the Text.