ArticlePloS one2015
2-methoxyestradiol induces vasodilation by stimulating NO release via PPARγ/PI3K/Akt pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Estrogen Degradation Metabolites: Some Effects on Heart Mitochondria.Journal of xenobiotics · 2025Article
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- PPARγ in Atherosclerotic Endothelial Dysfunction: Regulatory Compounds and PTMs.International journal of molecular sciences · 2023Review
- Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells.Nutrients · 2022Article
- Understanding the Role of Estrogen Receptor Status in PRODH/POX-Dependent Apoptosis/Survival in Breast Cancer Cells.Biology · 2021Review
- Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2019Review
- Effects of the Catechol and Methoxy Metabolites of 17β-Estradiol on Nitric Oxide Production by Ovine Uterine Artery Endothelial Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2019Article
- 2-Methoxyestradiol Attenuates Angiotensin II-Induced Hypertension, Cardiovascular Remodeling, and Renal Injury.Journal of cardiovascular pharmacology · 2019Article
- A Systems Pharmacology-Based Study of the Molecular Mechanisms of San Cao Decoction for Treating Hypertension.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Tumor necrosis factor alfa and interleukin 1 alfa induced phosphorylation and degradation of inhibitory kappa B alpha are regulated by estradiol in endometrial cells.Turkish journal of obstetrics and gynecology · 2018Article
- Apolipoprotein A1 mimetic peptide ATI-5261 reverses arterial stiffness at late pregnancy and early postpartum in a COMTClinical hypertension · 2018Article
- Obesity, estrogens and adipose tissue dysfunction - implications for pulmonary arterial hypertension.Pulmonary circulationReview
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 detected in HUVECs and the antagonist GW9662 or the transfection with specific PPARγ siRNA inhibited 2-ME-induced eNOS and Akt phosphorylation, leading to the impairment of NO production and vasodilation. In conclusion, 2-ME induces vasodilation by stimulating NO release. These actions may be mediated by PPARγ and the subsequent activation of Akt/eNOS cascade in vascular endothelial cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.