ArticleJournal of the American Heart Association2018
SMAD4 Deficiency Leads to Development of Arteriovenous Malformations in Neonatal and Adult Mice.
Article in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Molecular-genetic mechanisms of cerebral arteriovenous malformations: A systematic review of germline, somatic and experimental evidence.Neurosurgical review · 2026Pooled it
- Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Pooled it
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Modeling Somatic Second-Hit Mutations in Novel Mouse Models of Hereditary Hemorrhagic Telangiectasia.bioRxiv : the preprint server for biology · 2026Article
- Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations.Theranostics · 2026Article
- Characterization of microvessels in the human forehead dermis using intravascular dual perfusion and immunofluorescence staining.Scientific reports · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Chorordin-like 1 inhibits pancreatic cancer cell migration and invasion: involvement of the BMP4/SMAD pathway.Frontiers in oncology · 2025Article
- Endothelial-to-Mesenchymal Transition in an Hereditary Hemorrhagic Telangiectasia-like Pediatric Case of Multiple Pulmonary Arteriovenous Malformations.International journal of molecular sciences · 2024Article
- ANG2 Blockade Diminishes Proangiogenic Cerebrovascular Defects Associated With Models of Hereditary Hemorrhagic Telangiectasia.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Executive summary of the 14th HHT international scientific conference.Angiogenesis · 2023Article
- Article
- BMP10 functions independently from BMP9 for the development of a proper arteriovenous network.Angiogenesis · 2023Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
- Neuropilin-1 deficiency in vascular smooth muscle cells is associated with hereditary hemorrhagic telangiectasia arteriovenous malformations.JCI insight · 2022Article
- The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function.Cellular and molecular life sciences : CMLS · 2022Review
- An update on preclinical models of hereditary haemorrhagic telangiectasia: Insights into disease mechanisms.Frontiers in medicine · 2022Review
- Cellular loci involved in the development of brain arteriovenous malformations.Frontiers in human neuroscience · 2022Review
- Recent progress understanding pathophysiology and genesis of brain AVM-a narrative review.Neurosurgical review · 2021Review
- Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing.Journal of visualized experiments : JoVE · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Background Hereditary hemorrhagic telangiectasia ( HHT ) is a rare genetic vascular disorder caused by mutations in endoglin ( ENG ), activin receptor-like kinase 1 ( ACVRL 1; ALK 1), or SMAD 4. Major clinical symptoms of HHT are arteriovenous malformations ( AVM s) found in the brain, lungs, visceral organs, and mucosal surface. Animal models harboring mutations in Eng or Alk1 recapitulate all of these HHT clinical symptoms and have been useful resources for studying mechanisms and testing potential drugs. However, animal models representing SMAD 4 mutations have been lacking. The goal of this study is to evaluate Smad4-inducible knockout ( iKO ) mice as an animal model of HHT and compare the phenotypes with other established HHT animal models. Methods and Results Global Smad4 deletion was induced at neonatal and adult stages, and hemoglobin levels, gastrointestinal hemorrhage, and presence of aberrant arteriovenous connections were examined. Neonatal Smad4- iKO mice exhibited signs of gastrointestinal bleeding and AVM s in the brain, intestine, nose, and retina. The radial expansion was decreased, and AVM s were detected on both distal and proximal retinal vasculature of Smad4- iKO s. Aberrant smooth muscle actin staining was observed in the initial stage AVM s and their connecting veins, indicating abnormal arterial flow to veins. In adult mice, Smad4 deficiency caused gastrointestinal bleeding and AVM s along the gastrointestinal tract and wounded skin. HHT -related phenotypes of Smad4- iKO s appeared to be comparable with those found in Alk1- iKO and Eng- iKO mice. Conclusions These data further confirm that SMAD signaling is crucial for normal arteriovenous network formation, and Smad4- iKO will be an alternative animal model of AVM research associated with HHT .
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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.