ArticleThe Journal of experimental medicine2020
Cerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Molecular Pathways and Circulating Biomarkers in Cerebral Cavernous Malformations-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm.International journal of molecular sciences · 2025Pooled it
- Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.Journal of neuroinflammation · 2026Article
- Endothelial estrogen receptor alpha (ESR1) regulates cerebral cavernous malformation pathogenesis via MEKK3-KLF signaling pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- TIE2 links MEKK3-KLF2/4 and PI3K signaling in cerebral cavernous malformation.The Journal of experimental medicine · 2026Article
- Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice.Disease models & mechanisms · 2026Article
- ML364 ameliorates NLRP3-induced inflammatory response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Stc1-expressing myofibroblasts are a developmentally distinct lineage cleared through apoptosis in the neonatal lung.Cell reports · 2026Article
- Single-cell sequencing insights into the transcriptional landscape of cerebral cavernous malformations.Angiogenesis · 2025Review
- The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities.Clinical reviews in allergy & immunology · 2025Review
- Common and distinct circulating microRNAs in four neurovascular disorders.Biochemistry and biophysics reports · 2025Article
- Focused ultrasound augments the delivery and penetration of model therapeutics into cerebral cavernous malformations.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Clinical and molecular landscape of paediatric cerebral and spinal cavernous malformations.Brain communications · 2025Article
- Hyaluronic acid turnover controls the severity of cerebral cavernous malformations in bioengineered human micro-vessels.APL bioengineering · 2024Article
- mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.Stroke · 2023Article
- Circulating Plasma miRNA Homologs in Mice and Humans Reflect Familial Cerebral Cavernous Malformation Disease.Translational stroke research · 2023Article
- Release of STK24/25 suppression on MEKK3 signaling in endothelial cells confers cerebral cavernous malformation.JCI insight · 2023Article
- Plasma metabolites with mechanistic and clinical links to the neurovascular disease cavernous angioma.Communications medicine · 2023Article
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
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30 authors at 8 institutions in 4 countries.
Funding
Abstract
Cerebral cavernous malformations (CCMs) form following loss of the CCM protein complex in brain endothelial cells due to increased endothelial MEKK3 signaling and KLF2/4 transcription factor expression, but the downstream events that drive lesion formation remain undefined. Recent studies have revealed that CCM lesions expand by incorporating neighboring wild-type endothelial cells, indicative of a cell nonautonomous mechanism. Here we find that endothelial loss of ADAMTS5 reduced CCM formation in the neonatal mouse model. Conversely, endothelial gain of ADAMTS5 conferred early lesion genesis in the absence of increased KLF2/4 expression and synergized with KRIT1 loss of function to create large malformations. Lowering versican expression reduced CCM burden, indicating that versican is the relevant ADAMTS5 substrate and that lesion formation requires proteolysis but not loss of this extracellular matrix protein. These findings identify endothelial secretion of ADAMTS5 and cleavage of versican as downstream mechanisms of CCM pathogenesis and provide a basis for the participation of wild-type endothelial cells in lesion formation.
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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.