2-methoxyestradiol induces vasodilation by stimulating NO release via PPARγ/PI3K/Akt pathway

PloS One
Weiyu ChenXiaodong Fu

Abstract

The endogenous estradiol metabolite 2-methoxyestradiol (2-ME) reduces atherosclerotic lesion formation, while the underlying mechanisms remain obscure. In this work, we investigated the vasodilatory effect of 2-ME and the role of nitric oxide (NO) involved. In vivo studies using noninvasive tail-cuff methods showed that 2-ME decreased blood pressure in Sprague Dawley rats. Furthermore, in vitro studies showed that cumulative addition of 2-ME to the aorta caused a dose- and endothelium-dependent vasodilation. This effect was unaffected by the pretreatment with the pure estrogen receptor antagonist ICI 182,780, but was largely impaired by endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or by phosphoinositide 3-kinase (PI3K) inhibitor wortmannin (WM). Moreover, 2-ME(10-7 ∼10-5 M)enhanced phosphorylation of Akt and eNOS and promoted NO release from cultured human umbilical endothelial cells (HUVECs). These effects were blocked by PI3K inhibitor WM, or by the transfection with Akt specific siRNA, indicating that endothelial Akt/eNOS/NO cascade plays a crucial role in 2-ME-induced vasodilation. The peroxisome proliferator-activated receptor γ (PPARγ) mRNA and protein expression were detect...Continue Reading

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Citations

Feb 18, 2016·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Yongfu ZhangXiaodong Fu
Sep 4, 2015·Journal of Cellular Biochemistry·Stephan ReumannAvudaiappan Maran
Dec 28, 2019·International Journal of Molecular Sciences·Stevan P Tofovic, Edwin K Jackson
Mar 7, 2019·Journal of Cardiovascular Pharmacology·Eman SalahStevan P Tofovic
Jul 30, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Chongyang MaXueqian Wang

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Methods Mentioned

BETA
Reverse Transcription-Polymerase Chain Reaction
tension
PCR
transfection
Assay

Software Mentioned

BP Processing Software

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