Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.

We investigated whether microRNA-145 (miR-145) has a cardioprotective effect in a rabbit model of myocardial infarction (MI) and in H9c2 rat cardiomyoblasts. Rabbits underwent 30 min of coronary occlusion, followed by 2 days or 2 wk of reperfusion. Control microRNA (control group; 2.5 nmol/kg, n = 10) or miR-145 (miR-145 group, 2.5 nmol/kg, n = 10) encapsulated in liposomes was intravenously administered immediately after the start of reperfusion. H9c2 rat cardiomyoblasts were transfected with miR-145. The MI size was significantly smaller in the miR-145 group than in the control group at 2 days and 2 wk post-MI. miR-145 had improved the cardiac function and remodeling at 2 wk post-MI. These effects were reversed by chloroquine. Western blot analysis showed that miR-145 accelerated the transition of LC3B I to II and downregulated p62/SQSTM1 at 2 days or 2 wk after MI, but not at 4 wk, and activated Akt in the ischemic area at 2 days after MI. miR-145 inhibited the growth of H9c2 cells, accelerated the transition of LC3B I to II, and increased phosphorylated Akt in the H9c2 cells at 2 days after miR-145 transfection. Antagomir-145 significantly abolished the morphological change, the transition of LC3B I to II, and the increased phosphorylated Akt induced by miR-145 in H9c2 cells. We determined fibroblast growth factor receptor substrate 2 mRNA to be a target of miR-145, both in an in vivo model and in H9c2 cells. In conclusion, post-MI treatment with miR-145 protected the heart through the induction of cardiomyocyte autophagy by targeting fibroblast growth factor receptor substrate 2.

GLP-1 has been reported to be cardioprotective against ischemia-reperfusion injury. We aimed to examine the effect of alogliptin, which may produce GLP-1, on ischemia-reperfusion injury and its mechanisms. Rabbits were fed a normal chow (control group) and a chow containing alogliptin (2 mg·kg·d: alogliptin-L group and 20 mg·kg·d: alogliptin-H group) for 7 days. The rabbits underwent 30 minutes of coronary occlusion and 48 hours of reperfusion. Exendin (9-39) [5 or 50 μg/kg, i.v., alogliptin-H+exendin (9-39)-L group and alogliptin-H+exendin (9-39)-H group] or L-NAME (10 mg/kg, i.v., alogliptin-H+L-NAME group) was administered to the alogliptin-H group. Alogliptin dose-dependently reduced the infarct size, which was partially blocked by exendin (9-39), but completely blocked by L-NAME. Exendin (9-39) or L-NAME alone did not affect the infarct size for themselves. The left ventricular ejection fraction and ±dP/dt were higher in the alogliptin-L group and alogliptin-H group than in the control group. Alogliptin increased the serum NOx and plasma GLP-1 levels, and those levels inversely correlated with the infarct size. Alogliptin upregulated the expressions of phosphorylated (p)-Akt and p-eNOS, which were inhibited by exendin (9-39) and L-NAME, respectively. In conclusion, alogliptin protects the heart against ischemia-reperfusion injury through GLP-1 receptor-dependent and receptor-independent pathways which involve nitric oxide production in rabbits.

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