m6A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury.

Reperfusion therapy after acute myocardial infarction can induce myocardial ischemia-reperfusion injury (IRI). Novel evidence has illustrated that N6-methyladenosine (m6A) modification modulates the myocardial IRI progression. Here, our study focuses on the role of m6A methyltransferase fat mass and obesity-associated protein (FTO) in myocardial ischemia/reoxygenation injury and explores potential regulatory mechanisms. Results discovered that FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Functionally, FTO overexpression attenuated the H/R-induced apoptosis and inflammation of cardiomyocytes. Mechanistically, methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP-qPCR) assay and RIP assay revealed that Yap1 mRNA acted as the target of FTO in cardiomyocytes. Moreover, FTO uninstalled the methylation of Yap1 mRNA, and enforced the stability of Yap1 mRNA. Taken together, our study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which may provide a new approach to improve myocardial IRI.

Naringenin alleviates myocardial ischemia reperfusion injury by enhancing the myocardial miR-126-PI3K/AKT axis in streptozotocin-induced diabetic rats.

Ischemic heart disease (IHD) is a leading cause of death in patients with type 1 diabetes. The key to treating IHD is to restore blood supply to the ischemic myocardium, which inevitably causes myocardial ischemia reperfusion (MI/R) injury. Although naringenin (Nar) prevents MI/R injury, the role of Nar in diabetic MI/R (D-MI/R) injury remains to be elucidated. The PI3K/AKT signaling pathway and microRNA (miR)-126 have previously been shown to serve anti-MI/R injury roles. The present study aimed to investigate the protection of Nar against D-MI/R injury and the role of the miR-126-PI3K/AKT axis. Diabetic rats were treated distilled water or Nar (25 or 50 mg/kg, orally) for 30 days and then exposed to MI/R. The present results revealed that Nar alleviated MI/R injury in streptozotocin (STZ)-induced diabetic rats, as shown below: the reduction myocardial enzymes levels was measured using spectrophotometry, the increase of cardiac viability was detected by MTT assay, the inhibition of myocardial oxidative stress was measured using spectrophotometry and the enhancement of cardiac function were recorded using a hemodynamic monitoring system. Furthermore, Nar upregulated the myocardial miR-126-PI3K/AKT axis in D-MI/R rats. These results indicated that Nar alleviated MI/R injury through upregulating the myocardial miR-126-PI3K/AKT axis in STZ-induced diabetic rats. The current findings revealed that Nar, as an effective agent against D-MI/R injury, may provide an effective approach in the management of diabetic IHD.