ArticleCardiovascular research2015
Oestrogen receptor alpha in pulmonary hypertension.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.American journal of respiratory and critical care medicine · 2017Trial
- Dauricine Mitigates Hypoxia Through Targeting ESR1, PIK3CA, and MTOR: A Network Pharmacology and Molecular Dynamics Simulation Investigation.Current issues in molecular biology · 2026Article
- Review
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- Female Fibroblast Activation Is Estrogen-Mediated in Sex-Specific 3D-Bioprinted Pulmonary Artery Adventitia Models.ACS biomaterials science & engineering · 2025Article
- New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review.Cureus · 2024Review
- Recent developments in connective tissue disease associated pulmonary arterial hypertension.International journal of cardiology. Congenital heart disease · 2024Review
- Pulmonary Hypertension and Hyperglycemia-Not a Sweet Combination.Diagnostics (Basel, Switzerland) · 2024Review
- Characterization of PANoptosis-related genes and the immune landscape in moyamoya disease.Scientific reports · 2024Article
- Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.Drug design, development and therapy · 2024Article
- SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.American journal of respiratory and critical care medicine · 2023Article
- Estrogen Receptor-α Exerts Endothelium-Protective Effects and Attenuates Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2023Article
- Review
- Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension.Chinese medicine · 2022Review
- Role of estrogen receptors in health and disease.Frontiers in endocrinology · 2022Review
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice.European journal of pharmacology · 2021Article
- 17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin.The Journal of clinical investigation · 2021Article
- Sex Hormones and Lung Inflammation.Advances in experimental medicine and biology · 2021Article
- Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes.Journal of pain research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
aimsPulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. METHODS AND
resultsBy immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung.
conclusionERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression.
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Registered trials
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.