G protein-coupled estrogen receptor regulates the KLF2-dependent eNOS expression by activating of Ca2+ and EGFR signaling pathway in human endothelial cells

2021 ◽  
pp. 114721
Author(s):  
Jin Song Park ◽  
Gi Ho Lee ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Tuyet Ngan Thai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
G Protein ◽  
Egfr Signaling ◽  
Human Endothelial Cells ◽  
Enos Expression ◽  
Egfr Signaling Pathway ◽  
G Protein Coupled

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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ziwei Tang ◽  
Qifu Li ◽  
Qingfeng Cheng ◽  
Mei Mei ◽  
Ying Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Inflammatory Response ◽  
G Protein ◽  
Mineralocorticoid Receptor ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Independent Manner ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

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.

scholarly journals A hypertension patient-derived iPSC model demonstrates a role for G protein-coupled estrogen receptor in hypertension risk and development

2020 ◽  
Vol 319 (5) ◽  
pp. C825-C838 ◽  
Author(s):  
Natalie C. Fredette ◽  
Eliyah Malik ◽  
Marah L. Mukhtar ◽  
Eric R. Prossnitz ◽  
Naohiro Terada
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
G Protein ◽  
Vascular Endothelial Cells ◽  
Association Studies ◽  
No Production ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
G Protein Coupled

Hypertension (HTN) is a polyfactorial disease that can manifest severe cardiovascular pathologies such as heart failure or stroke. Genome-wide association studies (GWAS) of HTN indicate that single-nucleotide polymorphisms (SNPs) contribute to increased risk for HTN and resistance to some HTN drug regimens (Hiltunen TP et al., J Am Heart Assoc 4: e001521, 2015; Le MT et al., PLoS One 8: e52062, 2013; McDonough CW et al., J Hypertens 31: 698–704, 2013; Vandell AG et al., Hypertension 60: 957–964, 2012). However, cellular mechanistic insights of such SNPs remain largely unknown. Using a bank of induced pluripotent stem cells (iPSCs) derived from patients with HTN and CRISPR/Cas9-mediated gene-editing approach, we investigated the effects of a female HTN risk-associated SNP (rs1154431) of the G protein-coupled estrogen receptor (GPER) (Bassuk SS, Manson JE., Clin Chem 60: 68–77, 2014) in vascular endothelial cells. Although GPER1 deletion reduced endothelial nitric oxide synthase (eNOS) activation in iPSC-derived endothelial cells (iECs), the polymorphism itself did not significantly affect eNOS and NO production in a comparison of isogenic hemizygous iECs expressing either normal (P16) or HTN-associated (L16) GPER. Interestingly, we demonstrate for the first time that GPER plays a role in regulation of adhesion molecule expression and monocyte adhesion to iECs. Moreover, the L16 iECs had higher expression of inflammation genes than P16 iECs, implying that the risk variant may affect carrier individuals through increased inflammatory activity. This study further indicates that iPSCs are a useful platform for exploring mechanistic insights underlying hypertension GWAS endeavors.

scholarly journals The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)

2015 ◽  
Vol 100 ◽  
pp. 309-320 ◽  
Author(s):  
Aldo Moreno-Ulloa ◽  
David Mendez-Luna ◽  
Ernesto Beltran-Partida ◽  
Carmen Castillo ◽  
Gustavo Guevara ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
G Protein ◽  
G Protein Coupled

scholarly journals G protein-coupled estrogen receptor inhibits vascular prostanoid production and activity

2015 ◽  
Vol 227 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Matthias R Meyer ◽  
Natalie C Fredette ◽  
Matthias Barton ◽  
Eric R Prossnitz
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Vascular Disease ◽  
Postmenopausal Women ◽  
G Protein ◽  
Prostanoid Receptor ◽  
Inflammatory Conditions ◽  
Prostanoid Production ◽  
Tnf Α ◽  
G Protein Coupled

Complications of atherosclerotic vascular disease, such as myocardial infarction and stroke, are the most common causes of death in postmenopausal women. Endogenous estrogens inhibit vascular inflammation-driven atherogenesis, a process that involves cyclooxygenase (COX)-derived vasoconstrictor prostanoids such as thromboxane A2. Here, we studied whether the G protein-coupled estrogen receptor (GPER) mediates estrogen-dependent inhibitory effects on prostanoid production and activity under pro-inflammatory conditions. Effects of estrogen on production of thromboxane A2were determined in human endothelial cells stimulated by the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α). Moreover,Gper-deficient (Gper−/−) and WT mice were fed a pro-inflammatory diet and underwent ovariectomy or sham surgery to unmask the role of endogenous estrogens. Thereafter, contractions to acetylcholine-stimulated endothelial vasoconstrictor prostanoids and the thromboxane-prostanoid receptor agonist U46619 were recorded in isolated carotid arteries. In endothelial cells, TNF-α-stimulated thromboxane A2production was inhibited by estrogen, an effect blocked by the GPER-selective antagonist G36. In ovary-intact mice, deletion ofGperincreased prostanoid-dependent contractions by twofold. Ovariectomy also augmented prostanoid-dependent contractions by twofold in WT mice but had no additional effect inGper−/−mice. These contractions were blocked by the COX inhibitor meclofenamate and unaffected by the nitric oxide synthase inhibitorl-NG-nitroarginine methyl ester. Vasoconstrictor responses to U46619 did not differ between groups, indicating intact signaling downstream of thromboxane-prostanoid receptor activation. In summary, under pro-inflammatory conditions, estrogen inhibits vasoconstrictor prostanoid production in endothelial cells and activity in intact arteries through GPER. Selective activation of GPER may therefore be considered as a novel strategy to treat increased prostanoid-dependent vasomotor tone or vascular disease in postmenopausal women.

scholarly journals G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice

2020 ◽  
Vol 14 ◽  
Author(s):  
Chun Zhang ◽  
Qiang Liu ◽  
Chun-Yang Yu ◽  
Feng Wang ◽  
Yu Shao ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Social Interaction ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
G Protein ◽  
Memory Functions ◽  
Mk 801 ◽  
Expression Levels ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

The role of estrogen receptors in neuroprotection and cognition has been extensively studied in humans over the past 20 years. Recently, studies have shifted their focus to the use of selective estrogen receptor modulators in the treatment of mental illnesses in the central nervous system. We conducted this study to test the behavioral changes shown by G protein-coupled estrogen receptor 1 knockout (GPER1 KO) and wild-type (WT) mice with MK-801-induced schizophrenia (SZ). GPER1 KO and WT mice received intraperitoneal injections of MK-801 for 14 continuous days. Behavioral, learning and memory, and social interaction changes were evaluated by using the IntelliCage system, open-field, three-chamber social interaction, and novel object recognition tests (NORT). The protein expression levels of the NR2B/CaMKII/CREB signaling pathway were tested via Western blot analysis. The KO SZ group was more likely to show impaired long-term learning and memory function than the WT SZ group. Learning and memory functions were also impaired in the KO Con group. MK-801 administration to the GPER1-KO and WT groups resulted in memory deficiencies and declining learning capabilities. GPER1 deficiency downregulated the expression levels of proteins related to the NR2B/CaMKII/CREB signaling pathway. Our study suggested that GPER1 played an important role in cognitive, learning, and memory functions in the MK-801-induced mouse model of SZ. The mechanism of this role might partially involve the downregulation of the proteins related to the NR2B/CaMKII/CREB signaling pathway. Further studies should focus on the effect of GPER1 on the pathogenesis of SZ in vivo and in vitro.

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