ArticleThe Journal of clinical investigation2021
17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 108 citations in OpenAlex.
- Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.American journal of respiratory and critical care medicine · 2024Trial
- Apelin analog treatment reverses severe pulmonary arterial hypertension and right ventricular heart failure.JCI insight · 2026Article
- The Apelin-APJ Axis in Heart Failure: Mechanistic Insights, Clinical Evidence, and Translational Challenges.Cardiovascular drugs and therapy · 2026Review
- Towards a Safe Pathway to Biological Parenthood for Pulmonary Arterial Hypertension.Pulmonary circulation · 2026Article
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- Context‑dependent duality of the apelin/elabela‑APJ system in diabetes and its complications (Review).International journal of molecular medicine · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Activation of α7nAChR prevents maladaptive right ventricular remodeling via inhibiting the recruitment of CCR2Respiratory research · 2026Article
- Cardiomyocyte NLRP3 signaling in right heart failure is sexually dimorphic via estrogen receptor α.bioRxiv : the preprint server for biology · 2026Article
- Ovarian hormones attenuate right ventricular remodeling in a rat model of pulmonary arterial hypertension.Biomechanics and modeling in mechanobiology · 2025Article
- Cardiomyocyte GC1 Mediates Estrogenic Angiogenesis in Right Heart Remodeling.Circulation research · 2025Article
- Sexually dimorphic role of estrogen receptor α in preserving right ventricular endothelial integrity.bioRxiv : the preprint server for biology · 2025Article
- What I Learned From the Study of Sex Differences in Pulmonary Hypertension: How Following the Data and the Kindness of Strangers Helped Me Overcome Self-Doubt and Imposter Syndrome.Pulmonary circulation · 2025Article
- What I Learned From the Study of Sex Differences in Pulmonary Hypertension: How Following the Data and the Kindness of Strangers Helped Me Overcome Self-Doubt and Imposter Syndrome.Pulmonary circulation · 2025Article
- Initial Body Weight as an Important Factor for Improving the Reliability and Translational Relevance of the Preclinical Monocrotaline-Induced Rat Pulmonary Hypertension Model.International journal of molecular sciences · 2025Article
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Transcriptional Signatures of the Right Ventricle in End-Stage Heart Failure.Pulmonary circulation · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α-null or ER-β-null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex.
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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.