PEDF Improves Cardiac Function in Rats with Acute Myocardial Infarction via Inhibiting Vascular Permeability and Cardiomyocyte Apoptosis

Abstract

Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF’s effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2

“…Recombinant PEDF-lentivirus (PEDF-LV) was prepared as described previously [15]. PEDF overexpression plasmids and the RNAi vector were packaged in 293T cells.…”

“…It is expressed in multiple tissues and exerts diverse physiological activities, for instance blocking angiogenesis and tumor growth, anti-inflammatory and anti-oxidation [12,13,14]. Our previous studies have declared that PEDF inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction, and PEDF protects against hypoxia-induced apoptosis and necroptosis via an anti-oxidative effect [15,16]. However, it is not known whether PEDF inhibits the activation of the NLRP3 inflammasome to protect against myocardial cell death in hypoxia cardiomyocytes.…”

Cardioprotective effect of Salvianolic acid B on acute myocardial infarction by promoting autophagy and neovascularization and inhibiting apoptosis

“…Zhang et al . demonstrated that cardiomyocyte apoptosis dominantly contributed to myocardial infarction, by reducing which pigment epithelium‐derived factor managed to prevent cardiac ischaemic injury . Furthermore, autophagy has been regarded as a causative factor for AMI.…”

Cardiac Shock Wave Therapy Attenuates Cardiomyocyte Apoptosis after Acute Myocardial Infarction in Rats

“…Studies have demonstrated that cardiomyocyte apoptosis takes place in heart samples from patients suffering from MI [2]. Inhibition of cardiomyocyte apoptosis MI-induced can lead to a decrease of the infarct size and an improvement of cardiac function [3][4][5]. Cardiac shock wave therapy (CSWT) is a novel approach that provides a new choice for severe CHD.…”