ArticleProceedings of the National Academy of Sciences of the United States of America2015
Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03589014 (Treat_CCM Clinical Trial A Multicenter Randomized Clinical Trial on Propranolol in Familial Cerebral Cavernous Malformation), which is not on this map. Cited by 72 papers.
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.
Treat_CCM Clinical Trial A Multicenter Randomized Clinical Trial on Propranolol in Familial Cerebral Cavernous Malformation
Who cites it
72 citing papers in PubMed, 122 citations in OpenAlex.
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- Human stem cell models in cerebral cavernous malformations.Stem cell research & therapy · 2026Review
- Identification of the adhesion GPCR ADGRL4/ELTD1 as a novel potential prognostic biomarker for cerebral cavernous malformation disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Endothelial-Mesenchymal transition in cerebrovascular diseases: molecular mechanisms and promising pharmacological strategies.Molecular biology reports · 2026Review
- Integration of artificial intelligence and high-content screening enabled identification of drugs for long-term treatment of cerebral cavernous malformation disease.bioRxiv : the preprint server for biology · 2025Article
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis.APL bioengineering · 2025Review
- Intravital Imaging of Disease Mechanisms in a Mouse Model of CCM Skin Lesions-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Review
- Epigenetic regulation by polycomb repressive complex 1 promotes cerebral cavernous malformations.EMBO molecular medicine · 2024Article
- PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer.Clinical science (London, England : 1979) · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease.bioRxiv : the preprint server for biology · 2024Article
- Current and Future Treatment Options for Cerebral Cavernous Malformations.Stroke (Hoboken, N.J.) · 2024Review
- Comprehensive CCM3 Mutational Analysis in Two Patients with Syndromic Cerebral Cavernous Malformation.Translational stroke research · 2024Article
- Permissive role of vascular endothelium in fibrosis: focus on the kidney.American journal of physiology. Cell physiology · 2024Review
- Review
- Impaired retinoic acid signaling in cerebral cavernous malformations.Scientific reports · 2023Article
- Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation.The Journal of experimental medicine · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences. At present, the only recommended treatment of CCM is surgical. Because surgery is often not applicable, pharmacological treatment would be highly desirable. We describe here a murine model of the disease that develops after endothelial-cell-selective ablation of the CCM3 gene. We report an early, cell-autonomous, Wnt-receptor-independent stimulation of β-catenin transcription activity in CCM3-deficient endothelial cells both in vitro and in vivo and a triggering of a β-catenin-driven transcription program that leads to endothelial-to-mesenchymal transition. TGF-β/BMP signaling is then required for the progression of the disease. We also found that the anti-inflammatory drugs sulindac sulfide and sulindac sulfone, which attenuate β-catenin transcription activity, reduce vascular malformations in endothelial CCM3-deficient mice. This study opens previously unidentified perspectives for an effective pharmacological therapy of intracranial vascular cavernomas.
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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.