ArticleCardiovascular research2022
Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- An Ancient Founder GDF2 Variant Potentially Causes Semi-Dominant Non-Syndromic Pulmonary Arterial Hypertension.Clinical genetics · 2026Article
- Tumor-Induced PDPNInternational journal of molecular sciences · 2026Article
- Article
- Activin Signaling Inhibitors in Pulmonary Hypertension: A State-of-the-Art Review.Pulmonary circulation · 2026Review
- BMP9 Modulates IL-33 Signaling to Mitigate EndMT in Pulmonary Arterial Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Disrupting BMP/TGF-β Signaling: Modulation of AQP1 and TGFB1 in Human Pulmonary Microvascular Endothelial Cells.Comprehensive Physiology · 2025Article
- BMP9 knockout impairs pulmonary vessel muscularisation and confers aberrant tamoxifen sensitivity.Angiogenesis · 2025Article
- Atrial cardiomyopathy: From healthy atria to atrial failure. A clinical consensus statement of the Heart Failure Association of the ESC.European journal of heart failure · 2025Article
- BMP9 regulates the endothelial secretome to drive pulmonary hypertension.bioRxiv : the preprint server for biology · 2025Article
- SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- Characterization of microvessels in the human forehead dermis using intravascular dual perfusion and immunofluorescence staining.Scientific reports · 2025Article
- BMP9 enhances osteogenic differentiation in rheumatoid arthritis: a potential therapeutic approach.Journal of translational medicine · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.Breathe (Sheffield, England) · 2025Review
- BMP-9 mediates fibroproliferation in fibrodysplasia ossificans progressiva through TGF-β signaling.EMBO molecular medicine · 2025Article
- Updates on the Pathogenesis and Therapeutic Approaches for Hereditary Hemorrhagic Telangiectasia.Current vascular pharmacology · 2025Review
- Article
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsBMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension, but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10. METHODS AND
resultsSingle- and double-knockout mice for Bmp9 (constitutive) and/or Bmp10 (tamoxifen inducible) were generated. Single-knock-out (KO) mice developed no obvious age-dependent phenotype when compared with their wild-type littermates. However, combined deficiency in Bmp9 and Bmp10 led to vascular defects resulting in a decrease in peripheral vascular resistance and blood pressure and the progressive development of high-output heart failure and pulmonary hemosiderosis. RNAseq analysis of the lungs of the double-KO mice revealed differential expression of genes involved in inflammation and vascular homeostasis. We next challenged these mice to chronic hypoxia. After 3 weeks of hypoxic exposure, Bmp10-cKO mice showed an enlarged heart. However, although genetic deletion of Bmp9 in the single- and double-KO mice attenuated the muscularization of pulmonary arterioles induced by chronic hypoxia, we observed no differences in Bmp10-cKO mice. Consistent with these results, endothelin-1 levels were significantly reduced in Bmp9 deficient mice but not Bmp10-cKO mice. Furthermore, the effects of BMP9 on vasoconstriction were inhibited by bosentan, an endothelin receptor antagonist, in a chick chorioallantoic membrane assay.
conclusionsOur data show redundant roles for BMP9 and BMP10 in cardiovascular homeostasis under normoxic conditions (only combined deletion of both Bmp9 and Bmp10 was associated with severe defects) but highlight specific roles under chronic hypoxic conditions. We obtained evidence that BMP9 contributes to chronic hypoxia-induced pulmonary vascular remodelling, whereas BMP10 plays a role in hypoxia-induced cardiac remodelling in mice.
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