LAUSR

Numerous microRNAs (miRs) are abnormally expressed in response to hypoxia‐induced myocardial damage. Herein, miR‐34c‐5p as a potential pharmaco‐target was investigated in a mouse model of chronic intermittent hypoxia (CIH)‐induced myocardial damage. A mouse model of myocardial damage was established using CIH with 7% or 21% O2 alternating 60 s for 12 h/day, 21% O2 for 12 h/day. AntagomiR‐34c‐5p (20 nM/0.1 ml; once a week for 12 weeks) was used as a miR‐34c‐5p inhibitor in a mouse model with tail‐vein injection. In another experiment, mice were administrated with Sirt1 activator SRT1720 (50 mg/kg/day) by intraperitoneal injection. Gene Expression Omnibus database showed a significant upregulation of miR‐34c‐5p expression in the ischemic myocardium of male mice. In CIH‐stimulated mice, miR‐34c‐5p expression was also significantly increased compared with normal mice. Treatment of antagomiR‐34c‐5p significantly restrained CIH‐triggered myocardial apoptosis. After administration of antagomiR‐34c‐5p or Sirt1 activator SRT1720, cardiac hypertrophy and oxidative stress were attenuated in CIH‐stimulated mice. We also found sirtuin 1 (Sirt1) as a direct target of miR‐34c‐5p, which was able to mediate Sirt1 protein expression in cardiomyocytes. AntagomiR‐34c‐5p injection markedly elevated Sirt1 protein expression in CIH‐stimulated mice. AntagomiR‐34c‐5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH‐stimulated mice.