1. Academic Validation
  2. CTRP3 alleviates myocardial ischemia/reperfusion injury in mice through activating LAMP1/JIP2/JNK pathway

CTRP3 alleviates myocardial ischemia/reperfusion injury in mice through activating LAMP1/JIP2/JNK pathway

  • Int Immunopharmacol. 2022 Jun;107:108681. doi: 10.1016/j.intimp.2022.108681.
Yanbin Song 1 Yunqing Zhang 2 Zhaofei Wan 3 Junqiang Pan 4 Feng Gao 5 Fei Li 5 Jing Zhou 5 Junmin Chen 5
Affiliations

Affiliations

  • 1 Department of Cardiovasology, Yan'an University Affiliated Hospital, Yan'an 716000, China. Electronic address: yanbin_song1@163.com.
  • 2 Department of Pathology, Yan'an University Affiliated Hospital, Yan'an 716000, China.
  • 3 Department of Cardiology, the Second AffiliatedHospital of Xi'an Jiaotong University, Xi'an 710038, China.
  • 4 Department of Cardiology, Xi'an Central Hospital, Xi'an 710061, China.
  • 5 Department of Cardiovasology, Yan'an University Affiliated Hospital, Yan'an 716000, China.
Abstract

Myocardial ischemia reperfusion (I/R) injury is an important complication of myocardial infarction reperfusion therapy, and no effective treatment has been identified. Based on preexisting evidence, C1q/tumor necrosis factor-related protein 3 (CTRP3) has been reported to be closely associated with myocardial dysfunction. In this study, we found that CTRP3 was downregulated in acute coronary syndrome (ACS) patients and myocardial I/R mice. Silence of CTRP3 aggravated cardiac systolic function due to I/R of mice, while CTRP3 overexpression ameliorated cardiac function. Moreover, overexpression of CTRP3 improved I/R inhibitory effects on the levels of creatinine phosphokinase (CPK), Lactate Dehydrogenase (LDH) and cardiac troponin-I (cTn-I), myocardial infarction area, the intensity of the 3-nitrotyrosine (3-NT), Apoptosis and protein levels of LAMP1, JNK-Interacting Protein-2 (JIP-2) and JNK, while these effects could be exacerbated by downregulation of CTRP3. Co-IP experiments could identify physical interactions between CTRP3 and lysosomal-associated membrane protein 1 (LAMP1) and Numb and JIP2. LAMP1 silence aggravated the inhibition effects of I/R on JIP2 and JNK protein expression, CPK, LDH and cTn-I levels and Caspase-3 activity, while overexpression of LAMP1 recovered these inhibition effects of I/R. JNK Inhibitor (SP600125) could reverse the inhibitory effects of CTRP3 overexpression on CPK, LDH, cTn-I, myocardial infarction, strong positive staining for 3-NT and Apoptosis. These findings demonstrated that CTRP3 protected against injury caused by myocardial I/R through activating LAMP1/JIP2/JNK pathway to attenuate myocardial injury, improve left ventricular function, decrease myocardial infarction, and reduce myocardial Apoptosis.

Keywords

Apoptosis; CTRP3; LAMP1/JIP2/JNK pathway; Myocardial infarction; Myocardial ischemia/reperfusion injury.

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