ArticleAngiogenesis2012
BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway: implications for hereditary hemorrhagic telangiectasia type II.
Article in Angiogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Nitazoxanide activates BMP9-ALK1-SMAD signaling cascade and improves HHT vascular pathology.bioRxiv : the preprint server for biology · 2026Article
- Hemoptysis caused by hereditary hemorrhagic telangiectasia: A case report and literature review.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Article
- Blood flow regulatesbioRxiv : the preprint server for biology · 2024Article
- Endothelial tip/stalk cell selection requires BMP9-induced βMolecular biology of the cell · 2023Article
- The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function.Cellular and molecular life sciences : CMLS · 2022Review
- Review of treatment and therapeutic targets in brain arteriovenous malformation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Mutations in EPHB4 cause human venous valve aplasia.JCI insight · 2021Article
- The role of mural cells in hemorrhage of brain arteriovenous malformation.Brain hemorrhages · 2021Article
- Article
- Correcting Smad1/5/8, mTOR, and VEGFR2 treats pathology in hereditary hemorrhagic telangiectasia models.The Journal of clinical investigation · 2020Article
- Chemotropic signaling by BMP7 requires selective interaction at a key residue in ActRIIA.Biology open · 2019Article
- Hypoxia promotes differentiation of adipose-derived stem cells into endothelial cells through demethylation of ephrinB2.Stem cell research & therapy · 2019Article
- Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.Neuron · 2019Article
- Effect of Transcriptional Regulator ID3 on Pulmonary Arterial Hypertension and Hereditary Hemorrhagic Telangiectasia.International journal of vascular medicine · 2019Review
- Article
- TGF-β Signaling in Control of Cardiovascular Function.Cold Spring Harbor perspectives in biology · 2018Review
- Tacrolimus rescues the signaling and gene expression signature of endothelial ALK1 loss-of-function and improves HHT vascular pathology.Human molecular genetics · 2017Article
- ALK1 signaling in development and disease: new paradigms.Cellular and molecular life sciences : CMLS · 2017Review
- Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease.BioMed research international · 2017Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
ALK1 (ACVRL1) is a member of the TGFβ receptor family and is expressed predominantly by arterial endothelial cells (EC). Mutations in ACVRL1 are responsible for hereditary hemorrhagic telangiectasia type 2 (HHT2), a disease manifesting as fragile vessels, capillary overgrowth, and numerous arterio-venous malformations. Arterial EC also express EphrinB2, which has multiple roles in vascular development and angiogenesis and is known to be reduced in ACVRL1 knockout mice. Using an in vitro angiogenesis model we find that the Alk1 ligand BMP9 induces EphrinB2 in EC, and this is entirely dependent on expression of Alk1 and at least one of the co-receptors BMPRII or ActRII. BMP9 induces both ID1 and ID3, and both are necessary for full induction of EphrinB2. Loss of Alk1 or EphrinB2 results in increased arterial-venous anastomosis, while loss of Alk1 but not EphrinB2 results in increased VEGFR2 expression and enhanced capillary sprouting. Conversely, BMP9 blocks EC sprouting and this is dependent on Alk1, BMPRII/ActRII and ID1/ID3. Finally, notch signaling overcomes the loss of Alk1-restoring EphrinB2 expression in EC, and curbing excess sprouting. Thus, in an in vitro model of HHT2, loss of Alk1 blocks BMP9 signaling, resulting in reduced EphrinB2 expression, enhanced VEGFR2 expression, and misregulated EC sprouting and anastomosis.
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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.