ArticleBlood2022
Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Molecular Pathways and Circulating Biomarkers in Cerebral Cavernous Malformations-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.Journal of neuroinflammation · 2026Article
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 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
- A bismuth-based nanoplatform with synergistic fibrin/NET disruption and antioxidant/anti-inflammatory capabilities for enhanced thrombolysis and prevention of deep vein thrombosis recurrence.Journal of nanobiotechnology · 2025Article
- Association of Quality of Life Domains and Clinical Symptoms in Patients With Familial Cerebral Cavernous Malformation.Journal of the American Heart Association · 2025Article
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Antithrombotic therapy and cavernoma bleeding: does vascular border zone localization matter?Frontiers in surgery · 2025Article
- Intravital Imaging of Disease Mechanisms in a Mouse Model of CCM Skin Lesions-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Review
- Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation.Nature cardiovascular research · 2024Article
- Neutrophil extracellular traps worsen clotting and neuroinflammation in cavernomas.Nature cardiovascular research · 2024Article
- Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease.bioRxiv : the preprint server for biology · 2024Article
- Transcriptomic signatures of individual cell types in cerebral cavernous malformation.Cell communication and signaling : CCS · 2024Article
- Circulating biomarkers in familial cerebral cavernous malformation.EBioMedicine · 2024Article
- mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.Stroke · 2023Article
- Inflammatory Mechanisms in a Neurovascular Disease: Cerebral Cavernous Malformation.Brain sciences · 2023Review
- Dysregulated Hemostasis and Immunothrombosis in Cerebral Cavernous Malformations.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.
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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.