ArticleThe Journal of clinical investigation2021
Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 57 citations in OpenAlex.
- 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
- Aspirin Use and the Risk of Symptomatic Hemorrhage in Patients With Cerebral Cavernous Malformations and Ischemic Cerebrovascular Disease.Stroke (Hoboken, N.J.) · 2026Article
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice.Disease models & mechanisms · 2026Article
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- The neurobiological regulatory mechanism of brain edema.Frontiers in cellular neuroscience · 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
- Clinical outcomes of immunosuppressive therapy in patients with seronegative anti-PLA2R antibodies and PLA2R-related membranous nephropathy.Clinical and experimental nephrology · 2025Article
- Single-cell sequencing insights into the transcriptional landscape of cerebral cavernous malformations.Angiogenesis · 2025Review
- Article
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- Integrative multi-omics analysis identifies key genes and colocalized signals associated with colorectal cancer risk.BMC cancer · 2025Article
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Neuroinflammation and hypoxia promote astrocyte phenotypic transformation and propel neurovascular dysfunction in brain arteriovenous malformation.Journal of neuroinflammation · 2025Article
- Development of perivascular astrocyte processes.Frontiers in neuroscience · 2025Review
- Clinical and molecular landscape of paediatric cerebral and spinal cavernous malformations.Brain communications · 2025Article
- Large language models assisted multi-effect variants mining on cerebral cavernous malformation familial whole genome sequencing.Computational and structural biotechnology journal · 2024Article
- Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation.Nature cardiovascular research · 2024Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilized HIF-1α in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.
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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.