BACKGROUND: ischemia-reperfusion (I/R) is a consequence of restored blood supply after myocardial infarction. Myocardial I/R injury can be alleviated by reducing autophagy in heart tissue. MicroRNA-34a (miR-34a) has been shown to regulate autophagy in a renal model of I/R, but it is not known whether it can protect cardiac tissues from I/R injury. This study investigated how miR-34a protects myocardial cells from I/R injury by inhibiting autophagy via regulation of tumor necrosis factor α (TNFα). METHODS: we constructed an I/R model in vivo using Langendorff perfusion, and we constructed an in vivo model by treating neonatal rat cardiomyocytes (NRCMs) with hypoxia-reoxygenation (H/R method). Transfected adenoviral-overexpressed miR-34a mimics and controlled NRCMs after H/R. We analyzed cell viability using the MTT assay and a cell counting kit-8 (CCK-8) assay. Changes in the rate of apoptosis were detected by flow cytometry. We investigated the effect mechanisms of miR-34a with Western blot and luciferase assays. RESULTS: miR-34a expression decreased after in vivo reperfusion of the myocardial cells and heart tissues of neonatal rats. MiR-34a reduced apoptosis of the NRCMs and autophagy levels, simultaneously, after H/R injury. Further, miR-34a decreased the expression of Lc3-II and p62, indicating that miR-34a reduces myocardial I/R injury by decreasing TNFα expression. CONCLUSION: miR-34a can inhibit autophagy levels after I/R by targeting TNFα, thereby reducing myocardial injury.
BACKGROUND:ischemia-reperfusion (I/R) is a consequence of restored blood supply after myocardial infarction. Myocardial I/R injury can be alleviated by reducing autophagy in heart tissue. MicroRNA-34a (miR-34a) has been shown to regulate autophagy in a renal model of I/R, but it is not known whether it can protect cardiac tissues from I/R injury. This study investigated how miR-34a protects myocardial cells from I/R injury by inhibiting autophagy via regulation of tumor necrosis factor α (TNFα). METHODS: we constructed an I/R model in vivo using Langendorff perfusion, and we constructed an in vivo model by treating neonatal rat cardiomyocytes (NRCMs) with hypoxia-reoxygenation (H/R method). Transfected adenoviral-overexpressed miR-34a mimics and controlled NRCMs after H/R. We analyzed cell viability using the MTT assay and a cell counting kit-8 (CCK-8) assay. Changes in the rate of apoptosis were detected by flow cytometry. We investigated the effect mechanisms of miR-34a with Western blot and luciferase assays. RESULTS:miR-34a expression decreased after in vivo reperfusion of the myocardial cells and heart tissues of neonatal rats. MiR-34a reduced apoptosis of the NRCMs and autophagy levels, simultaneously, after H/R injury. Further, miR-34a decreased the expression of Lc3-II and p62, indicating that miR-34a reduces myocardial I/R injury by decreasing TNFα expression. CONCLUSION:miR-34a can inhibit autophagy levels after I/R by targeting TNFα, thereby reducing myocardial injury.
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Keywords:
MicroARN-34a; autophagie; autophagy; dommage d’ischémie et reperfusion; facteur nécrosant des tumeurs α; ischemia and reperfusion injury; microRNA-34a; tumor necrosis factor α
Authors: Md Nasim Haidar; M Babul Islam; Utpala Nanda Chowdhury; Md Rezanur Rahman; Fazlul Huq; Julian M W Quinn; Mohammad Ali Moni Journal: IET Syst Biol Date: 2020-04 Impact factor: 1.615