ArticleAmerican journal of physiology. Lung cellular and molecular physiology2008
Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions.
Article in American journal of physiology. Lung cellular and molecular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 138 citations in OpenAlex.
- BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Bidirectional Crosstalk Between Sleep and Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension.Journal of translational medicine · 2025Review
- Mas1 Receptor Activation is Necessary and Sufficient to Transduce ACE2 Effect in PAH, But Ang(1-7) Alone is Insufficient.Pulmonary circulation · 2025Article
- A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma.Frontiers in medicine · 2024Article
- Article
- A potential adverse role for leptin and cardiac leptin receptor in the right ventricle in pulmonary arterial hypertension: effect of metformin is BMPR2 mutation-specific.Frontiers in medicine · 2023Article
- Non-Muscle MLCK Contributes to Endothelial Cell Hyper-Proliferation through the ERK Pathway as a Mechanism for Vascular Remodeling in Pulmonary Hypertension.International journal of molecular sciences · 2022Article
- The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure.Circulation research · 2022Review
- New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis.Circulation research · 2022Review
- Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension.Antioxidants & redox signaling · 2021Review
- Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension.Cells · 2021Review
- Review
- 'There and Back Again'-Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension.Genes · 2020Review
- Pluripotent hematopoietic stem cells augment α-adrenergic receptor-mediated contraction of pulmonary artery and contribute to the pathogenesis of pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Article
- An Emotional Molecular Pathway in Pulmonary Hypertension-Alternative Complement System.American journal of respiratory and critical care medicine · 2020Article
- Adverse effects of BMPR2 suppression in macrophages in animal models of pulmonary hypertension.Pulmonary circulation · 2019Article
- Bone Morphogenetic Proteins in Vascular Homeostasis and Disease.Cold Spring Harbor perspectives in biology · 2018Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Familial pulmonary arterial hypertension (PAH) is associated with mutations in bone morphogenetic protein type II receptor (BMPR2). Many of these mutations occur in the BMPR2 tail domain, leaving the SMAD functions intact. To determine the in vivo consequences of BMPR2 tail domain mutation, we created a smooth muscle-specific doxycycline-inducible BMPR2 mutation with an arginine to termination mutation at amino acid 899. When these SM22-rtTA x TetO(7)-BMPR2(R899X) mice had transgene induced for 9 wk, starting at 4 wk of age, they universally developed pulmonary vascular pruning as assessed by fluorescent microangiography. Approximately one-third of the time, the induced animals developed elevated right ventricular systolic pressures (RVSP), associated with extensive pruning, muscularization of small pulmonary vessels, and development of large structural pulmonary vascular changes. These lesions included large numbers of macrophages and T cells in their adventitial compartment as well as CD133-positive cells in the lumen. Small vessels filled with CD45-positive and sometimes CD3-positive cells were a common feature in all SM22-rtTA x TetO(7)-BMPR2(R899X) mice. Gene array experiments show changes in stress response, muscle organization and function, proliferation, and apoptosis and developmental pathways before RVSP increases. Our results show that the primary phenotypic result of BMPR2 tail domain mutation in smooth muscle is pulmonary vascular pruning leading to elevated RVSP, associated with early dysregulation in multiple pathways with clear relevance to PAH. This model should be useful to the research community in examining early molecular and physical events in the development of PAH and as a platform to validate potential treatments.
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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.