2025 Volume 66 Issue 4 Pages 628-638
Evidence suggests that autophagy plays a crucial role in myocardial ischemia/reperfusion (I/R) injury. Renalase (RNLS) plays a protective role in cardiovascular diseases, including myocardial ischemia/reperfusion injury (MI/RI). Therefore, we used both in vivo and in vitro I/R models to monitor autophagy in the cardiomyocytes by exposing H9c2 cells to oxygen and glucose deprivation/reoxygenation (OGD/R) and subjecting rats to I/R, respectively. Wistar rats (male, 8 weeks, n = 27) were randomly divided into a Sham group, I/R + Vehicle group, and I/R + recombinant renalase protein (Re-RNLS) group. An MI/RI model was induced by left anterior descending artery ligation/release, TTC-Evans blue double staining was utilized to evaluate the area of myocardial infarction and ischemic area 24 hours after the operation, and plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities, plasma RNLS, epinephrine, and dopamine concentrations were detected by ELISA. H9c2 cells were treated with OGD/R serum and pretreated with Re-RNLS, chloroquine (CQ), and MK2206. Western blotting detected protein expression changes in LC3 autophagosomes were monitored by immunofluorescence, and cell death was determined by flow cytometry. The level of RNLS in serum was significantly increased during MI/RI in rats, and Re-RNLS significantly reduced myocardial infarct size after I/R surgery (24.6 ± 4.1% versus 11.2 ± 1.2%). RNLS deficiency aggravated the OGD/R injury in H9c2 cells, and Re-RNLS inhibited the expression of LC3 and Beclin-1 in H9c2 cells subjected to OGD/R, thereby reducing autophagosome formation. Re-RNLS activated the Akt/mTOR pathway of H9c2 cells to play a cytoprotective role. RNLS protects against MI/RI injury by inhibiting autophagy through activating the Akt/mTOR pathway.
