Inhibition of MicroRNA-122-5p Relieves Myocardial Ischemia-Reperfusion Injury via SOCS1.

OBJECTIVE: Evidence has shown that microRNA (miR)-122-5p is a diagnostic biomarker of acute myocardial infarction. Here, we aimed to uncover the functions of miR-122-5p in the pathological process of myocardial ischemia-reperfusion injury (MI/RI). METHODS: An MI/RI model was established by left anterior descending coronary artery ligation in mice. The levels of miR-122-5p, suppressor of cytokine signaling-1 (SOCS1), phosphorylation of Janus kinase 2 (p-JAK2), and signal transducers and activators of transcription (p-STAT3) in the myocardial tissues of mice were measured. Downregulated miR-122-5p or upregulated SOCS1 recombinant adenovirus vectors were injected into mice before MI/RI modeling. The cardiac function, inflammatory response, myocardial infarction area, pathological damage, and cardiomyocyte apoptosis in the myocardial tissues of mice were evaluated. Cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) injury and cardiomyocyte biological function was tested upon transfection of miR-122-5p inhibitor. The target relation between miR-122-5p and SOCS1 was evaluated. RESULTS: miR-122-5p expression and p-JAK2 and p-STAT3 expression were high, and SOCS1 expression was low in the myocardial tissues of MI/RI mice. Decreasing miR-122-5p or increasing SOCS1 expression inactivated the JAK2/STAT3 pathway to alleviate MI/RI by improving cardiac function and reducing inflammatory reaction, myocardial infarction area, pathological damage, and cardiomyocyte apoptosis in mice. Silencing of SOCS1 reversed depleted miR-122-5p-induced cardioprotection for MI/RI mice. In vitro experiments revealed that the downregulation of miR-122-5p induced proliferative, migratory, and invasive capabilities of H/R cardiomyocytes while inhibiting apoptosis. Mechanically, SOCS1 was a target gene of miR-122-5p. CONCLUSION: Our study summarizes that inhibition of miR-122-5p induces SOCS1 expression, thereby relieving MI/RI in mice.

Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1.

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.