Resveratrol alleviates preeclampsia-like symptoms in rats through a mechanism involving the miR-363-3p/PEDF/VEGF axis

Abstract

Preeclampsia (PE) is a hypertension-associated disease, and resveratrol (RES) is a polyphenol recognized to present beneficial effects in cardiovascular disease including hypertension. Recently, attentions have come to the therapeutic effect of RES in PE, but the underlying molecular mechanisms remain largely unknown. This study sought to delineate the mechanistic basis regarding bioinformatically identified miR-363-3p/PEDF/VEGF axis for RES treatment in PE. PE-like symptoms were induced in vivo in Sprague-Dawley rats by intraperitoneal injection with Ng-nitro-L-arginine methyl ester (L-NAME), and hypoxia was induced in vitro in trophoblasts by CoCl₂. Accordingly, RES was found to enhance viability, migration, angiogenesis, and to repress the apoptosis of hypoxic trophoblasts in vitro. Furthermore, in vivo experiments noted that RES alleviated placental injury and promoted angiogenesis in rats with PE-like symptoms in vivo by increasing VEGF via promoting miR-363-3p-mediated PEDF suppression. Collectively, RES ameliorates PE by upregulating VEGF through miR-363-3p-mediated PEDF downregulation, the mechanism of which may be of promising significance to augment RES efficacy in PE treatment.

Keywords: MicroRNA-363-3p; Pigment epithelium-derived factor; Placental angiogenesis; Preeclampsia; Resveratrol; Trophoblast; Vascular endothelial growth factor.