ArticleThe Journal of experimental medicine2010
Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 343 citations in OpenAlex.
- Rho-associated kinase inhibitors in cerebral cavernous malformations: a preclinical systematic review.Neurosurgical review · 2026Pooled it
- Safety and efficacy of atorvastatin for rebleeding in cerebral cavernous malformations (AT CASH EPOC): a phase 1/2a, randomised placebo-controlled trial.The Lancet. Neurology · 2025Trial
- Clinical pharmacology and tolerability of REC-994, a redox-cycling nitroxide compound, in randomized phase 1 dose-finding studies.Pharmacology research & perspectives · 2024Trial
- Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial.Translational stroke research · 2020Trial
- Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial.Neurosurgery · 2019Trial
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pediatric Familial Cerebral Cavernous Malformation Associated With a Novel KRIT1 Initiation-Region Frameshift Variant.Molecular genetics & genomic medicine · 2026Article
- Article
- Endothelial Nucleoporin93 (Nup93) Maintains Vascular Homeostasis via Sun1-Dependent Regulation of RhoA/ROCK Activity.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.Journal of neuroinflammation · 2026Article
- Article
- Unveiling a Novel Molecular Interaction and Pro-Metastatic Signaling Cascades Driven by KRIT1.International journal of molecular sciences · 2026Article
- Possible correlation between KRIT1 variant and non-atherosclerotic vasculopathy resulting in ischemic stroke.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- The effect of statins on the risk of bleeding in cerebral cavernous malformations: A systematic review and meta-analysis.Surgical neurology international · 2026Review
- Familial Cerebral Cavernous Malformations: Pathophysiology, Genetics, Biomarkers, and Treatment Perspectives.Journal of neurochemistry · 2026Review
- Single-cell sequencing insights into the transcriptional landscape of cerebral cavernous malformations.Angiogenesis · 2025Review
- Focused ultrasound-microbubble treatment arrests the growth and formation of cerebral cavernous malformations.Nature biomedical engineering · 2025Article
- High-throughput differentiation of human blood vessel organoids reveals overlapping and distinct functions of the cerebral cavernous malformation proteins.Angiogenesis · 2025Article
- Cerebral Cavernous Malformation: From Genetics to Pharmacotherapy.Brain and behavior · 2025Review
147 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cell-cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell-cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell-cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1(+/-) or Ccm2(+/-) mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1(+/-) and Ccm2(+/-) mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1-CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak.
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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.