The Effects of Progranulin in a Rat Model of Acute Myocardial Ischemia/Reperfusion are Mediated by Activation of the P13K/Akt Signaling Pathway

• Published in: Medical science monitor. Basic research Vol. 25; pp. 229 - 237
• Main Authors: Alyahya, Asma Mohammed, Al-Masri, Abeer, Hersi, Ahmad, El Eter, Eman, Husain, Sufia, Lateef, Rahmatunnesa, Mawlana, Ola H
• Format: Journal Article
• Language: English
• Published: United States International Scientific Literature, Inc 07-11-2019
• Subjects: Adipokines - pharmacology; Animal Studies; Animals; Apoptosis - drug effects; Atherosclerosis - drug therapy; Chromones - pharmacology; Disease Models, Animal; Male; Morpholines - pharmacology; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - drug therapy; Myocardium - pathology; Myocytes, Cardiac - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Progranulins - metabolism; Progranulins - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Reperfusion Injury - drug therapy; Signal Transduction - drug effects
• ISSN: 2325-4416; 2325-4394; 2325-4416
• DOI: 10.12659/msmbr.916258

BACKGROUND Progranulin is an adipokine, encoded by the progranulin (GRN) gene. Progranulin is expressed in atherosclerosis, but its effects in cardiac ischemia and reperfusion injury are unknown. Therefore, this study aimed to investigate the effects of progranulin in a rat model of acute myocardial ischemia/reperfusion (MI/R) injury in vivo. MATERIAL AND METHODS The model of acute MI/R injury was established in male Wistar rats by ligation of the left anterior descending (LAD) coronary artery for 30 minutes and reperfusion for 60 minutes. Before modeling, one group was treated with progranulin (0.03 µg/kg), and one group was treated with the P13K/Akt inhibitor, LY294002 (3 mg/kg). Left ventricular function (LV) was monitored, including the LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and changes in LV pressure. At the end of the study, blood and myocardial tissue were examined. Cardiac biochemical markers, histopathology, gene expression, and apoptosis were analyzed. RESULTS Progranulin improved cardiac function following acute MI/R injury and significantly improved recovery of cardiac contractility and LVSP. Progranulin significantly reduced myocyte apoptosis, inflammation, and tissue edema, and was highly expressed in cardiac tissue following MI/R injury. The cardioprotective effect of progranulin was reduced by blocking the P13K/Akt signaling pathway. CONCLUSIONS In the rat model of acute MI/R injury, progranulin had a protective effect on cardiac function and morphology, associated with activation of the P13K/Akt signaling pathway. The mechanisms of the anti-apoptotic, anti-inflammatory, and inotropic effects of progranulin in the setting of acute MI/R injury require further in vivo studies.