Modulation of PTEN by hexarelin attenuates coronary artery ligation-induced heart failure in rats

Abstract

Background/aim: Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. However, itscardioprotective effect against heart failure (HF) is yet to be explained. This study investigated the therapeutic role of hexarelin and themechanisms underlying its cardioprotective effects against coronary artery ligation (CAL)-induced HF in rats.Materials and methods: Rats with four weeks of permanent CAL, induced myocardial infarction, and HF were randomly separated intofour groups: the control group (Ctrl), sham group (Sham), hexarelin treatment group (HF + Hx), and heart failure group (HF). The ratswere treated with subcutaneous injection of hexarelin (100 µg/kg) in the treatment group or saline in the other groups twice a day for30 days. Left ventricular (LV) function, oxidative stress, apoptosis, molecular analyses, and cardiac structural and pathological changesin rats were assessed.Results: The treatment of HF rats with hexarelin significantly induced the upregulation of phosphatase and tensin homologue (PTEN)expression and inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) to significantlyimprove LV function, ameliorate myocardial remodeling, and reduce oxidative stress.Conclusion: These findings indicate that hexarelin attenuates CAL-induced HF in rats by ameliorating myocardial remodeling, LVdysfunction, and oxidative stress via the upmodulation of PTEN signaling and downregulation of the Akt/mTOR signaling pathway.