The role of progranulin in ischemic heart disease and its related risk factors.

Cardiovascular disease, in particular, ischemic heart disease, is the leading cause of mortality worldwide. Obesity and its related disorders are linked to cardiovascular events. Adipose tissue is an active endocrine organ that secretes bioactive molecules termed adipokines, which play an important role in heart function. Progranulin, one of the adipokines, plays a crucial role in health and disease. In relation to heart disease, progranulin has shown anti-inflammatory activity in the vascular endothelium and its deletion has exacerbated the atherosclerotic process. Progranulin binds to apo-lipoprotein A-1 and forms a complex attenuating pro-inflammatory activity of progranulin and stabilizing atherosclerotic plaques. The adipokine may have an athero-protective role by increasing nitric oxide level in the vascular endothelium by enhancing endothelial nitric oxide synthase phosphorylation, enhancing reverse cholesterol transport, and exerting an antithrombotic effect. Furthermore, PGRN exhibits protective properties in an acute ischemia-reperfusion injury. However, Progranulin has a pro-inflammatory action linked with cardiovascular risk factors, such as metabolic syndrome and type two diabetes. The review at hand sheds light on the interesting role that progranulin plays in ischemic heart disease and its related risk factors.

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

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.