ArticleCirculation2018
SMAD4 Prevents Flow Induced Arteriovenous Malformations by Inhibiting Casein Kinase 2.
Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 125 citations in OpenAlex.
- Targeting KIT prevents brain arteriovenous malformations driven by ALK1-deficient angiogenic endothelial cells.The Journal of clinical investigation · 2026Article
- Loss of Smad4 drives vascular malformations via c-KIT-dependent high-fluid shear stress mimicry.The Journal of clinical investigation · 2026Article
- Decreased Endothelial Cell Retinoic Acid Signaling Accelerates Progression of Single Ventricle Pulmonary Vascular Malformations.JACC. Basic to translational science · 2026Article
- Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Review
- Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction.Basic research in cardiology · 2026Article
- A 15-layer multi-omics analysis of gastric cancer ecotypes provides therapeutic insights.Cell reports. Medicine · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- Mothers against decapentaplegic homolog 4 as a proteomic hub in vascular remodeling and residual cardiovascular risk.World journal of cardiology · 2026Article
- Modeling Somatic Second-Hit Mutations in Novel Mouse Models of Hereditary Hemorrhagic Telangiectasia.bioRxiv : the preprint server for biology · 2026Article
- Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy.Nature biomedical engineering · 2026Article
- Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations.Theranostics · 2026Article
- Bidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c.Journal of nanobiotechnology · 2025Article
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways.Biochemical Society transactions · 2025Review
- The Role of Somatic Mutation in Hereditary Hemorrhagic Telangiectasia Pathogenesis.Journal of clinical medicine · 2025Review
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder that causes arteriovenous malformations (AVMs). Mutations in the genes encoding Endoglin ( ENG) and activin-receptor-like kinase 1 ( AVCRL1 encoding ALK1) cause HHT type 1 and 2, respectively. Mutations in the SMAD4 gene are present in families with juvenile polyposis-HHT syndrome that involves AVMs. SMAD4 is a downstream effector of transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP) family ligands that signal via activin-like kinase receptors (ALKs). Ligand-neutralizing antibodies or inducible, endothelial-specific Alk1 deletion induce AVMs in mouse models as a result of increased PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) signaling. Here we addressed if SMAD4 was required for BMP9-ALK1 effects on PI3K/AKT pathway activation.
methodsThe authors generated tamoxifen-inducible, postnatal, endothelial-specific Smad4 mutant mice ( Smad4
resultsWe found that loss of endothelial Smad4 resulted in AVM formation and lethality. AVMs formed in regions with high blood flow in developing retinas and other tissues. Mechanistically, BMP9 signaling antagonized flow-induced AKT activation in an ALK1- and SMAD4-dependent manner. Smad4
conclusionsOur study reveals SMAD4 as an essential effector of BMP9-10/ALK1 signaling that affects AVM pathogenesis via regulation of CK2 expression and PI3K/AKT1 activation.
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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.