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, its cardioprotective effect against heart failure (HF) is yet to be explained. This study investigated the therapeutic role of hexarelin and the mechanisms 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 into four groups: the control group (Ctrl), sham group (Sham), hexarelin treatment group (HF + Hx), and heart failure group (HF). The rats were treated with subcutaneous injection of hexarelin (100 µg/kg) in the treatment group or saline in the other groups twice a day for 30 days. Left ventricular (LV) function, oxidative stress, apoptosis, molecular analyses, and cardiac structural and pathological changes in 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 significantly improve 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, LV dysfunction, and oxidative stress via the upmodulation of PTEN signaling and downregulation of the Akt/mTOR signaling pathway.

Molecular characterization of the immediate wound response of the solitary ascidian Polycarpa mytiligera

“…Despite variability of the independent replicates, likely because of challenges with tissue isolation (Experimental Procedures), we identified similarities in gene expression, including overexpression of the genes encoding BMP1 , growth hormone secretagogue receptor ( GHSR ) and a putative serine proteinase inhibitor ( PI ). These genes had robust expression following injury, and were previously shown to have roles in tissue repair and wound healing in other organisms 18‐21 . In addition, these genes were differentially expressed in the distal vs. the proximal siphon pieces (Figure 2), showing increased expression of BMP1 , GHSR , and PI at 24 hpa in the necrotic distal fragments and low expression levels in the proximal fragments at this time point, comparable to that of controls.…”

“…These genes had robust expression following injury, and were previously shown to have roles in tissue repair and wound healing in other organisms. [18][19][20][21] In addition, these genes were differentially expressed in the distal vs. the proximal siphon pieces (Figure 2), showing increased expression of BMP1, GHSR, and PI at 24 hpa in the necrotic distal fragments and low expression levels in the proximal fragments at this time point, comparable to that of controls. These results indicated that there were similarities in injury-induced gene expression at different injury sites.…”

Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment

“…In vivo infarct therapy effect was evaluated by measuring the infarct size, which is considered to be a critical indicator to evaluate the cardiac damage (Ramachandra et al, 2020 ). Coronary artery ligation is a widely used method to establish the AMI rat model for the evaluation of the in vivo infarct therapy effect, because it is more clinically relevant to imitate the clinical status of patients (Agbo et al, 2019 ). MTP/RGD-CAL/TAN NS exhibited better infarct size reduction effect compared with MTP-CAL/TAN NS and CAL/TAN NS, suggesting the modification effect of the double modification of MTP-131 and RGD peptide.…”

Cardioprotective role of myocardial endothelial nitric oxide synthase and serum nitric oxide induced by hexarelin in rats with myocardial infarction-induced heart failure

“…The exertion of those reported cardioprotective effects by hexarelin is achieved by binding to either cardiac non-growth hormone secretagogue receptor CD36 or the growth hormone secretagogue receptor-1a (2). Some of the beneficial cardiovascular functions of hexarelin include its antiatherosclerotic functions (3), suppression of cardiac fibrosis (4,5), anti-apoptotic effects (6,7), and cardiac output improvement (8)(9)(10).…”