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

Abstract

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

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling

“…[28][29][30] Mounting evidence shows that activation of Nrf2 protects against H/R-induced cardiac injury in vitro and myocardial ischemiareperfusion injury in vivo. [31][32][33][34] Various factors regulate Nrf2 activation during H/R-induced cardiac injury; however, the precise molecular mechanisms remain largely unknown. CTRP12 has been reported to exert a key role in the regulation of Nrf2 activation.…”

Inhibition of microRNA-122 alleviates pyroptosis by targeting dual-specificity phosphatase 4 in myocardial ischemia/reperfusion injury

“…In the in vivo myocardial I/R model (60min LAD coronary artery ligation followed by reperfusion as previously shown [ 27 ]), according to the reported study, successful reperfusion was confirmed by the changes in the myocardium color and ECG [ 28 ]. Echocardiography suggested that compared with the sham surgery group, cardiac function deteriorated according to the parameters including decreased EF% and FS% as well as increased LVEDD, LVESD, LVEDV, and LVESV.…”

Hypoxia-treated umbilical mesenchymal stem cell alleviates spinal cord ischemia-reperfusion injury in SCI by circular RNA circOXNAD1/ miR-29a-3p/ FOXO3a axis

“…Several studies have previously reported the involvement of miR-29a-3p in ischemia/reperfusion-induced cell injury and its function in diverse disease context [ 33 ]. For example, nuclear factor erythroid-2 related factor 2 (NRF2) transcriptionally elevated the expression of miR-29a-3p and suppressed cardiomyocyte apoptosis, oxidative stress, and serum inflammation via suppressing CCNT2 in rats with myocardial ischemia reperfusion injury [ 34 ]. Shen and his colleagues suggested that overexpression of miR-29a-3p that delivered by bone marrow mesenchymal stem cells to target the expression of Ireb2 and consequently reduced the Fe 2+ level and inhibited ferroptosis in hepatic ischemia-reperfusion injury [ 35 ].…”