ArticleNature2013
EndMT contributes to the onset and progression of cerebral cavernous malformations.
Article in Nature, 2013. 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 313 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
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
313 citing papers in PubMed, 2 syntheses or guidelines pooled it, 478 citations in OpenAlex.
- Rho-associated kinase inhibitors in cerebral cavernous malformations: a preclinical systematic review.Neurosurgical review · 2026Pooled it
- A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm.International journal of molecular sciences · 2025Pooled it
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Loss of arap3 drives a cerebral cavernous malformation-like phenotype in zebrafish via Krit1 interaction and RhoA dysregulation.Development (Cambridge, England) · 2026Article
- CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.Journal of neuroinflammation · 2026Article
- 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
- DOT1L Drives Endothelial-to-Mesenchymal Transition and Fibrotic Vascular Remodeling via H3K79 Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- RNA-seq analysis reveals altered gene expression profiles in HMEC-1 cells overexpressing KRAS gene associated with brain arteriovenous malformation.Chinese neurosurgical journal · 2026Article
- APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β.Cell death discovery · 2026Article
- Long noncoding RNA SRRM2-AS1 mediates coronary artery damage in Kawasaki disease by promoting endothelial-to-mesenchymal transition.Clinical and experimental medicine · 2026Article
- Dual recruitment of two CCM2 molecules to KRIT1 suppresses KLF4 expression.Nature communications · 2026Article
- Multi-omic analysis identifies a multi-step pathology in a case of multiple chorangioma syndrome in monochorionic twins.Orphanet journal of rare diseases · 2026Article
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- YAP1::TFE3 mediates endothelial-to-mesenchymal plasticity in epithelioid hemangioendothelioma.Molecular oncology · 2026Article
- Endothelial-Mesenchymal transition in cerebrovascular diseases: molecular mechanisms and promising pharmacological strategies.Molecular biology reports · 2026Review
- Familial Cerebral Cavernous Malformations: Pathophysiology, Genetics, Biomarkers, and Treatment Perspectives.Journal of neurochemistry · 2026Review
- TGF-β in chronic kidney disease: a controversy for decades.Frontiers in immunology · 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
253 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral cavernous malformation (CCM) is a vascular dysplasia, mainly localized within the brain and affecting up to 0.5% of the human population. CCM lesions are formed by enlarged and irregular blood vessels that often result in cerebral haemorrhages. CCM is caused by loss-of-function mutations in one of three genes, namely CCM1 (also known as KRIT1), CCM2 (OSM) and CCM3 (PDCD10), and occurs in both sporadic and familial forms. Recent studies have investigated the cause of vascular dysplasia and fragility in CCM, but the in vivo functions of this ternary complex remain unclear. Postnatal deletion of any of the three Ccm genes in mouse endothelium results in a severe phenotype, characterized by multiple brain vascular malformations that are markedly similar to human CCM lesions. Endothelial-to-mesenchymal transition (EndMT) has been described in different pathologies, and it is defined as the acquisition of mesenchymal- and stem-cell-like characteristics by the endothelium. Here we show that endothelial-specific disruption of the Ccm1 gene in mice induces EndMT, which contributes to the development of vascular malformations. EndMT in CCM1-ablated endothelial cells is mediated by the upregulation of endogenous BMP6 that, in turn, activates the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling pathway. Inhibitors of the TGF-β and BMP pathway prevent EndMT both in vitro and in vivo and reduce the number and size of vascular lesions in CCM1-deficient mice. Thus, increased TGF-β and BMP signalling, and the consequent EndMT of CCM1-null endothelial cells, are crucial events in the onset and progression of CCM disease. These studies offer novel therapeutic opportunities for this severe, and so far incurable, pathology.
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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.