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Restoration of NRF2 attenuates myocardial ischemia reperfusion injury through mediating microRNA‐29a‐3p/CCNT2 axis

Accumulated studies have been implemented for comprehending the mechanism of myocardial ischemia reperfusion injury (MI/RI). Nuclear factor erythroid‐2 related factor 2 (NRF2)‐mediated transcription activity in MI/RI has not been completely interpreted from the perspective of microRNA‐29a‐3p (miR‐29a‐3p) and cyclin T2 (CCNT2). Therein, this study intends to decode the mechanism of NRF2/miR‐29a‐3p/CCNT2 axis in MI/RI. Rat MI/RI models were established by left anterior descending artery ligation. Rats were injected with NRF2 or CCNT2 overexpression plasmids or miR‐29a‐3p agomir to explore their effects on MI/RI. Hypoxia/reoxygenation (H/R) cardiomyocytes were established and transfected with restored NRF2 or miR‐29a‐3p or CCNT2 for further exploration of their roles. NRF2, miR‐29a‐3p, and CCNT2 expression in myocardial tissues in rats with MI/RI and in cardiomyocytes in H/R injury were detected. ChIP assay verified the relationship between miR‐29a‐3p and NRF2, and the bioinformatics software and dual‐luciferase reporter experiment verified the interaction between miR‐29a‐3p and CCNT2. NRF2 and miR‐29a‐3p were down‐regulated while CCNT2 was up‐regulated in myocardial tissues in rats with MI/RI and in H/R‐treated cardiomyocytes. Restoration of NRF2 or miR‐29a‐3p improved hemodynamics and myocardial injury and suppressed serum inflammation and cardiomyocyte apoptosis via CCNT2 in rats with MI/RI. Upregulation of NRF2 or miR‐29a‐3p inhibited LDH and CK‐MB activities, oxidative stress, and apoptosis and promoted viability of cardiomyocytes with H/R injury. NRF2 bound to the promoter of miR‐29a‐3p and CCNT2 was targeted by miR‐29a‐3p. This study elucidates that up‐regulating NRF2 or miR‐29a‐3p attenuates MI/RI via inhibiting CCNT2, which may renew the existed knowledge of MI/RI‐related mechanism and provide a novel guidance toward MI/RI treatment.