ArticleCirculation research2020
Somatic Gain of KRAS Function in the Endothelium Is Sufficient to Cause Vascular Malformations That Require MEK but Not PI3K Signaling.
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06098872 (Pilot Study on the Efficacy of MEK1/MEK2 Inhibitor Trametinib in Patients With Surgical Unruptured Arteriovenous Malformations), which is not on this map. Cited by 81 papers, 2 of them syntheses that pooled it.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pilot Study on the Efficacy of MEK1/MEK2 Inhibitor Trametinib in Patients With Surgical Unruptured Arteriovenous Malformations
Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 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
- From Somatic Driver to Molecular Therapy in Retinal, Choroidal and Periocular Vascular Disease: Mosaicism, Targetable Pathways and Ocular Toxicity.International journal of molecular sciences · 2026Review
- A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modelling.Nature biomedical engineering · 2026Article
- Sirolimus outperforms alpelisib in models ofBlood vessels, thrombosis & hemostasis · 2026Article
- Mutant KRAS in brain endothelial cells promotes vascular inflammation and impairs vascular integrity in brain arteriovenous malformation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Trametinib for multiple non-ossifying fibromas due to KRAS mosaic mutations: two case reports.Communications medicine · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Decoding brain arteriovenous malformations: from genetic insights to modeling the vascular maze.Acta neuropathologica communications · 2026Review
- Pathogenic mechanism of extracranial arteriovenous malformations: insights from clinical, pathological, and genetic analyses.Virchows Archiv : an international journal of pathology · 2026Article
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- De novo twig-like middle cerebral artery after suspected M1 dissection in early childhood with coexisting KRAS-mutated brain arteriovenous malformation: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
- Endothelial oncogenic KRAS mutation drives the dynamics of microglia and macrophages in brain arteriovenous malformation.JCI insight · 2026Article
- Un-sweetening the deal: targeting glucose metabolism in brain arteriovenous malformations.EMBO molecular medicine · 2026Article
- Trametinib Decreased Intracerebral Hemorrhages and Endothelial-to-Mesenchymal Transition in KRASStroke · 2026Article
- KRAS-dependent glycolytic reprogramming of endothelial cells in sporadic arteriovenous malformations.EMBO molecular medicine · 2026Article
- Advances in genetics, signaling, and modeling of venous malformations.Frontiers in cardiovascular medicine · 2026Review
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Article
- Evaluating Animal Models of Arteriovenous Malformation and Intracerebral Aneurysm: A Mechanistic Approach.Stroke (Hoboken, N.J.) · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleWe previously identified somatic activating mutations in the
objectiveTo establish the first in vivo models of somatic KRAS gain of function in the endothelium in both mice and zebrafish to directly observe the phenotypic consequences of constitutive KRAS activity at a cellular level in vivo, and to test potential therapeutic interventions for arteriovenous malformations. METHODS AND
resultsUsing both postnatal and adult mice, as well as embryonic zebrafish, we demonstrate that endothelial-specific gain of function mutations in
conclusionsWe demonstrate that active KRAS expression in the endothelium is sufficient for brain arteriovenous malformations, even in the setting of uninjured adult vasculature. Furthermore, the finding that KRAS-dependent lesions are reversible in zebrafish suggests that MEK inhibition may represent a promising therapeutic treatment for arteriovenous malformation patients. Graphical Abstract: A graphical abstract is available for this article.
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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.