G Protein-Coupled Estrogen Receptor 1 (GPER1) Mediates Aldosterone-Induced Endothelial Inflammation in a Mineralocorticoid Receptor-Independent Manner.

Ziwei Tang,Qifu Li,Qingfeng Cheng,Ying Song,Shumin Yang,Zhihong Wang,Zhipeng Du,Mei Mei,Jinbo Hu,Wenwen He,Pawel Grzmil

doi:10.1155/2021/5575927

Abstract

Objective It has been increasingly appreciated that G protein-coupled estrogen receptor 1 (GPER1) mediates both proinflammatory and anti-inflammatory response of estrogen. It is also involved in some rapid vascular effects of aldosterone in a mineralocorticoid receptor (MR) independent manner. However, whether GPER1 mediates aldosterone-induced inflammation response in endothelial cells and its relationship with MR are yet undetermined and therefore require further explanation. Method Based on the hypothesis that GPER1 plays a role in the aldosterone-related vascular inflammation, the present study utilized a model of human umbilical vein endothelial cells transfected with MR siRNA and induced for inflammatory response with increasing concentration of aldosterone. Results It was discovered that induction of aldosterone had no effect on the expression of GPER1 but promoted the expression of MR. Suppression of MR did not influence GPER1 expression, and GPER1 was capable of mediating part of aldosterone-induced endothelial inflammatory response. This effect may involve phosphoinositide 3-kinases (PI3K) pathway signaling. Conclusion These findings not only demonstrated the role of GPER1 in aldosterone-induced vascular inflammation but also suggested an alternative for pharmaceutical treatment of hyperaldosteronism considering the unsatisfying effect on cardiovascular risks with MR antagonists.

Highlights

Accumulated evidence has demonstrated the role of aldosterone in vascular endothelial inflammation [1,2,3]
Since the role of G protein-coupled estrogen receptor 1 (GPER1) in aldosterone-induced inflammation or its interaction with mineralocorticoid receptor (MR) when stimulated by aldosterone has never been investigated before, in the present study, we investigated whether GPER1 contributed to the aldosterone-induced vascular inflammation
Human interleukin 1 beta (IL1β) ELISA kit was purchased from KeyGen Biotech, China (KGEHC002b). e anti-NOD, LRR, and pyrin domaincontaining protein 3 (NLRP-3); anti-IL-1β; anti-GPER1; and anti-MR antibodies were purchased from Abcam, UK. e second antibodies were purchased from KeyGen Biotech, China

Summary

Introduction

Accumulated evidence has demonstrated the role of aldosterone in vascular endothelial inflammation [1,2,3]. It is appreciated that binding and translocation of cytosolic mineralocorticoid receptor (MR) by aldosterone will lead to activation of reactive oxygen species (ROS) as well as mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathways [4, 5]. Is phenomenon sheds light on the role of nonMR receptors in the physiological regulation of aldosterone. Previous literature suggested that GPER1 was required for aldosterone-induced calcium influx and sodium/bicarbonate cotransporters activation as well as sodium proton exchange [9,10,11] in several nonvascular cell models. Gros et al [12] demonstrated that GPER1 contributed to the rapid activation of extracellular signal-regulated kinase (ERK) and apoptosis of aldosterone-induced vascular smooth muscle cells.

Methods

Results

Discussion

Conclusion