ArticleAmerican journal of respiratory and critical care medicine2015
Sex affects bone morphogenetic protein type II receptor signaling in pulmonary artery smooth muscle cells.
Article in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 81 citations in OpenAlex.
- Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.American journal of respiratory and critical care medicine · 2017Trial
- Hepatocyte growth factor may contribute to male protection against pulmonary arterial hypertension.Biology of sex differences · 2026Article
- The role of lactate metabolism and lactylation in pulmonary arterial hypertension.Respiratory research · 2025Review
- Pathophysiological Features of Remodeling in Vascular Diseases: Impact of Inhibitor of DNA-Binding/Differentiation-3 and Estrogenic Endocrine Disruptors.Medical sciences (Basel, Switzerland) · 2024Review
- Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions.Nature communications · 2024Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations.Journal of nanobiotechnology · 2024Article
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- Sex-biased TGFβ signalling in pulmonary arterial hypertension.Cardiovascular research · 2023Review
- New Drugs and Therapies in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Pathophysiology and new advances in pulmonary hypertension.BMJ medicine · 2023Review
- Molecular Pathways in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2022Review
- The Role of Thyroid Disorders, Obesity, Diabetes Mellitus and Estrogen Exposure as Potential Modifiers for Pulmonary Hypertension.Journal of clinical medicine · 2022Review
- Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension.Chinese medicine · 2022Review
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- The role of TGF-β or BMPR2 signaling pathway-related miRNA in pulmonary arterial hypertension and systemic sclerosis.Arthritis research & therapy · 2021Review
- 17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin.The Journal of clinical investigation · 2021Article
- Gene Mutation Annotation and Pedigree for Pulmonary Arterial Hypertension Patients in Han Chinese Patients.Global heart · 2021Article
- Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension.Frontiers in cardiovascular medicine · 2021Review
- Sex and Gender Differences in Lung Disease.Advances in experimental medicine and biology · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleMajor pulmonary arterial hypertension (PAH) registries report a greater incidence of PAH in women; mutations in the bone morphogenic protein type II receptor (BMPR-II) occur in approximately 80% of patients with heritable PAH (hPAH).
objectivesWe addressed the hypothesis that women may be predisposed to PAH due to normally reduced basal BMPR-II signaling in human pulmonary artery smooth muscle cells (hPASMCs).
methodsWe examined the BMPR-II signaling pathway in hPASMCs derived from men and women with no underlying cardiovascular disease (non-PAH hPASMCs). We also determined the development of pulmonary hypertension in male and female mice deficient in Smad1. MEASUREMENTS AND MAIN
resultsPlatelet-derived growth factor, estrogen, and serotonin induced proliferation only in non-PAH female hPASMCs. Female non-PAH hPASMCs exhibited reduced messenger RNA and protein expression of BMPR-II, the signaling intermediary Smad1, and the downstream genes, inhibitors of DNA binding proteins, Id1 and Id3. Induction of phospho-Smad1/5/8 and Id protein by BMP4 was also reduced in female hPASMCs. BMP4 induced proliferation in female, but not male, hPASMCs. However, small interfering RNA silencing of Smad1 invoked proliferative responses to BMP4 in male hPASMCs. In male hPASMCs, estrogen decreased messenger RNA and protein expression of Id genes. The estrogen metabolite 4-hydroxyestradiol decreased phospho-Smad1/5/8 and Id expression in female hPASMCs while increasing these in males commensurate with a decreased proliferative effect in male hPASMCs. Female Smad1(+/-) mice developed pulmonary hypertension (reversed by ovariectomy).
conclusionsWe conclude that estrogen-driven suppression of BMPR-II signaling in non-PAH hPASMCs derived from women contributes to a pro-proliferative phenotype in hPASMCs that may predispose women to PAH.
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