Markers of Endothelial Dysfunction Are Attenuated by Resveratrol in Preeclampsia

Abstract

Preeclampsia (PE) is characterized by great endothelial dysfunction, decreased nitric oxide (NO) bioavailability, and higher levels of arginase activity. In the present study, we investigated the potential modulatory effects of trans-resveratrol (RSV) on arginase and endothelial dysfunction biomarkers in endothelial cells exposed to plasma from patients with PE and healthy pregnant (HP) women, and umbilical arteries from patients with PE. Human umbilical vein endothelial cells (HUVECs) were incubated with pooled plasma from 10 HP or 10 PE pregnant women and RSV; umbilical arteries from patients with PE were incubated with RSV; intracellular NO and total reactive oxygen species (ROS) levels were assessed using a probe that interacted with these radicals; total arginase activity was evaluated measuring the urea produced; total antioxidant capacity was measured using the ferric reduction ability power (FRAP) assay; and endothelial dysfunction biomarkers were assessed using qPCR in endothelial cells and umbilical arteries. RSV increased NO levels and decreased total arginase activity in endothelial cells incubated with plasma from patients with PE. In addition, RSV increased total antioxidant capacity and downregulated endothelial dysfunction biomarkers, such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3, (CASP-3), in endothelial cells and umbilical arteries from PE patients. RSV treatment positively modulated the L-arginine–NO pathway, decreased arginase activity, and increased antioxidant capacity, in addition to downregulating endothelial dysfunction biomarkers.

A network pharmacology study on mechanism of resveratrol in treating preeclampsia via regulation of AGE-RAGE and HIF-1 signalling pathways

“…Previous studies have shown that RSV upregulates VEGF ( 36 ) and inhibits the release of sFlt-1 from the placenta ( 37 , 38 ). In addition, RSV could protect the trophoblast against oxidative stress ( 39 , 40 ) and improve vascular endothelial functions ( 41 – 43 ). A clinical trial showed that RSV is a safe and effective adjuvant of oral nifedipine to attenuate hypertensive symptoms among PE patients ( 44 ).…”

Aerobic Exercise-Mimetic Effects of Resveratrol on the Prevention of Vascular Endothelial Senescence

“…These signaling pathways regulate mitochondrial biogenesis, oxidative metabolism, and inflammation, which are important determinants of vascular function [23]. In recent years, there has been an increasing number of studies investigat- ing the potential of resveratrol to prevent vascular endothelial senescence [24]. These studies have provided evidence that resveratrol treatment can prevent cellular senescence in vascular endothelial cells by reducing oxidative stress and activating sirtuins [25].…”

The Role of Dietary Polyphenols in Pregnancy and Pregnancy-Related Disorders

“…Similar beneficiary effects was reported when mice and rats were treated with puerarin [71] and vitexin [90] in different PE models. Resveratrol showed positive effects on endothelial dysfunction induced in in vitro models [91][92][93]. This stilbenoid inhibited sFlt-1 release from human umbilical vein endothelial cells (HUVECs), placental explants, and primary cytotrophoblast and trophoblast HTR-8/SVneo cell line both under basal conditions or after stimulation with hypoxia or cytokines [91,92].…”

“…This stilbenoid inhibited sFlt-1 release from human umbilical vein endothelial cells (HUVECs), placental explants, and primary cytotrophoblast and trophoblast HTR-8/SVneo cell line both under basal conditions or after stimulation with hypoxia or cytokines [91,92]. HUVECs incubated with sera of PE patients showed increased expression of endothelial dysfunction marker mRNAs, such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3 (CAS-3) [93]. When incubated in the presence of resveratrol, mRNA expression levels were downregulated in HUVECs treated with PE sera [93].…”

“…HUVECs incubated with sera of PE patients showed increased expression of endothelial dysfunction marker mRNAs, such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3 (CAS-3) [93]. When incubated in the presence of resveratrol, mRNA expression levels were downregulated in HUVECs treated with PE sera [93]. Amelioration of PE symptoms by polyphenol treatment in PE animal models is thought to also be mediated through lowering of oxidative stress and inflammation [63][64][65][66]68,71,73,90].…”