ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- Mitochondrial Dysregulation and Molecular Signaling in Systemic Sclerosis Cardiac Disease: An Integrative Echocardiographic, Microvascular, and Biomarker Review.International journal of molecular sciences · 2026Review
- [Russian eligibility criteria for prescription of menopausal hormone therapy to patients with cardiovascular and metabolic diseases. Agreement document of RKO, ROAG, RAE, EAT, AFR, RNMOT, RAGG].Problemy endokrinologii · 2026Article
- Sex Differences in Pulmonary Hypertension and Associated Right Ventricular Dysfunction.The American journal of cardiology · 2026Article
- Cardiomyocyte GC1 Mediates Estrogenic Angiogenesis in Right Heart Remodeling.Circulation research · 2025Article
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension.American journal of physiology. Heart and circulatory physiology · 2024Article
- Clinical characteristics and survival analysis of class I pulmonary arterial hypertension.American journal of translational research · 2023Article
- β3 adrenergic agonism: A novel pathway which improves right ventricular-pulmonary arterial hemodynamics in pulmonary arterial hypertension.Physiological reports · 2023Article
- Compromised Cardiopulmonary Function in Fibulin-5 Deficient Mice.Journal of biomechanical engineering · 2022Article
- l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation.Pulmonary circulation · 2022Article
- Sex differences in right ventricular adaptation to pressure overload in a rat model.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- The Role of Thyroid Disorders, Obesity, Diabetes Mellitus and Estrogen Exposure as Potential Modifiers for Pulmonary Hypertension.Journal of clinical medicine · 2022Review
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension.Frontiers in cardiovascular medicine · 2021Review
- Current Understanding of the Right Ventricle Structure and Function in Pulmonary Arterial Hypertension.Frontiers in physiology · 2021Review
- Roles of Genetic Predisposition in the Sex Bias of Pulmonary Pathophysiology, as a Function of Estrogens : Sex Matters in the Prevalence of Lung Diseases.Advances in experimental medicine and biology · 2021Article
- The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study.Frontiers in medicine · 2021Article
- Direct Delivery of MicroRNA96 to the Lungs Reduces Progression of Sugen/Hypoxia-Induced Pulmonary Hypertension in the Rat.Molecular therapy. Nucleic acids · 2020Article
- Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism.Cardiovascular diagnosis and therapy · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction and failure. Paradoxically, women are more frequently diagnosed with PAH but have better RV systolic function and survival rates than men. The mechanisms by which sex differences alter PAH outcomes remain unknown. Here, we sought to study the role of estrogen in RV functional remodeling in response to PAH. The SU5416-hypoxia (SuHx) mouse model of PAH was used. To study the role of estrogen, female mice were ovariectomized and then treated with estrogen or placebo. SuHx significantly increased RV afterload and resulted in RV hypertrophy. Estrogen treatment attenuated the increase in RV afterload compared with the untreated group (effective arterial elastance: 2.3 ± 0.1 mmHg/μl vs. 3.2 ± 0.3 mmHg/μl), and this was linked to preserved pulmonary arterial compliance (compliance: 0.013 ± 0.001 mm(2)/mmHg vs. 0.010 ± 0.001 mm(2)/mmHg; P < 0.05) and decreased distal muscularization. Despite lower RV afterload in the estrogen-treated SuHx group, RV contractility increased to a similar level as the placebo-treated SuHx group, suggesting an inotropic effect of estrogen on RV myocardium. Consequently, when compared with the placebo-treated SuHx group, estrogen improved RV ejection fraction and cardiac output (ejection fraction: 57 ± 2% vs. 44 ± 2% and cardiac output: 9.7 ± 0.4 ml/min vs. 7.6 ± 0.6 ml/min; P < 0.05). Our study demonstrates for the first time that estrogen protects RV function in the SuHx model of PAH in mice directly by stimulating RV contractility and indirectly by protecting against pulmonary vascular remodeling. These results underscore the therapeutic potential of estrogen in PAH.
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