GPER inhibits diabetes-mediated RhoA activation to prevent vascular endothelial dysfunction

European Journal of Cell Biology
Zilin LiJincheng Liu

Abstract

The effect of estrogen receptors on diabetes-induced vascular dysfunction is critical, but ambiguous. Individuals with diabetic vascular disease may require estrogen receptor-specific targeted therapy in the future. The G protein-coupled estrogen receptor (GPER) has beneficial effects on vascular function. However, its fundamental mechanisms are unclear. The RhoA/Rho-kinase pathway contributes to diabetic vascular complications, whereas estrogen can suppress Rho-kinase function. Thus, we assumed that GPER inhibits diabetes-mediated RhoA activation to prevent vascular dysfunction. We further investigated the underlying mechanisms involved in this process. Vascular endothelial cells and ex vivo cultured ovariectomized (OVX) C57BL/6 mouse aortae were treated with high glucose (HG) alone or in combination with GPER agonist (G1). G1 treatment was also administered to OVX db/db mice for 8 weeks. An ex-vivo isovolumic myograph was used to analyze the endothelium-dependent vasodilation and endothelium-independent contraction of mouse aortae. Apoptosis, oxidative stress, and inflammation were attenuated in G1-pretreated vascular endothelial cells. G1 significantly decreased the phosphorylation of inhibitory endothelial nitric oxide (NO)...Continue Reading

References

Apr 14, 1999·Cell Death and Differentiation·A G Porter, R U Jänicke
Sep 5, 2002·Nature Reviews. Cancer·Suzanne Cory, Jerry M Adams
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Alyson J ProrockKlaus Ley
Oct 22, 2003·Journal of the American Society of Nephrology : JASN·Joan C KrepinskyJames W Scholey
Nov 5, 2003·Journal of Cellular and Molecular Medicine·Alexandrina Burlacu
Dec 4, 2003·Current Opinion in Cell Biology·Kelly M Boatright, Guy S Salvesen
Feb 12, 2005·Science·Chetana M RevankarEric R Prossnitz
Jul 22, 2005·Clinical Science·Casper G Schalkwijk, Coen D A Stehouwer
Mar 8, 2006·Nature Chemical Biology·Cristian G BologaEric R Prossnitz
Jul 15, 2006·Journal of Molecular and Cellular Cardiology·Peter F MountDavid A Power
Feb 14, 2007·Hypertension·Sergey DikalovDavid G Harrison
Jun 15, 2007·European Journal of Pharmacology·Guo-Sheng FuQiang Xia
Jul 27, 2007·Biochemical and Biophysical Research Communications·Masayuki SugimotoKozo Kaibuchi
Feb 12, 2008·Trends in Pharmacological Sciences·Eric R ProssnitzJeffrey B Arterburn
May 12, 2009·Nature Chemical Biology·Megan K DennisEric R Prossnitz
Aug 14, 2009·Expert Review of Neurotherapeutics·Naoki Sawada, James K Liao
Sep 2, 2009·Journal of Pharmacological Sciences·Yasuhiro TakenouchiKatsuo Kamata
Jan 12, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Brad R S BroughtonChristopher G Sobey
May 31, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Kimio SatohHiroaki Shimokawa
Jul 12, 2011·Vascular Pharmacology·Matthias R MeyerMatthias Barton
Jul 28, 2011·American Journal of Physiology. Endocrinology and Metabolism·Xuan YuGuichun Han
Sep 21, 2011·Future Cardiology·Michelle SurmaJianjian Shi
Feb 14, 2012·Life Sciences·Matthias R MeyerEric R Prossnitz

❮ Previous
Next ❯

Citations

Dec 13, 2018·EMBO Reports·Ernesto CortesArmando E Del Río Hernández
Aug 14, 2020·American Journal of Physiology. Cell Physiology·Natalie C FredetteNaohiro Terada
Jul 5, 2019·Pharmacology & Therapeutics·M Elizabeth MossIris Z Jaffe
May 6, 2021·British Journal of Pharmacology·Quynh Nhu DinhChristopher G Sobey

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis