ArticleProceedings of the National Academy of Sciences of the United States of America2013
Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Pooled it
- Exerkines in Cardiovascular-Kidney-Metabolic Syndrome: An Integrative Framework for Mechanisms and Therapeutic Implications-A Narrative Review.Reviews in cardiovascular medicine · 2026Review
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Decoding brain arteriovenous malformations: from genetic insights to modeling the vascular maze.Acta neuropathologica communications · 2026Review
- Matrix Gla Protein Expression in Pericytes and Myofibroblasts Contributes to Renal Fibrosis.The American journal of pathology · 2026Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- A Rare Case of Polymicrogyria in an Elderly Individual With Unique Polygenic Underlining.Cureus · 2024Article
- Mgp High-Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite-Mediated Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inhibition of endothelial histone deacetylase 2 shifts endothelial-mesenchymal transitions in cerebral arteriovenous malformation models.The Journal of clinical investigation · 2024Article
- Article
- Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis.The European respiratory journal · 2023Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
- Soluble Endoglin Stimulates Inflammatory and Angiogenic Responses in Microglia That Are Associated with Endothelial Dysfunction.International journal of molecular sciences · 2022Article
- The vascular protective effect of matrix Gla protein during kidney injury.Frontiers in molecular medicine · 2022Review
- Brain arteriovenous malformation in hereditary hemorrhagic telangiectasia: Recent advances in cellular and molecular mechanisms.Frontiers in human neuroscience · 2022Review
- Review of treatment and therapeutic targets in brain arteriovenous malformation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- Review
- Pronethalol decreases RBPJκ to reduce Sox2 in cerebral arteriovenous malformation.Vascular medicine (London, England) · 2020Article
- Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.Circulation research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cerebral arteriovenous malformations (AVMs) are common vascular malformations, which may result in hemorrhagic strokes and neurological deficits. Bone morphogenetic protein (BMP) and Notch signaling are both involved in the development of cerebral AVMs, but the cross-talk between the two signaling pathways is poorly understood. Here, we show that deficiency of matrix Gla protein (MGP), a BMP inhibitor, causes induction of Notch ligands, dysregulation of endothelial differentiation, and the development of cerebral AVMs in MGP null (Mgp(-/-)) mice. Increased BMP activity due to the lack of MGP induces expression of the activin receptor-like kinase 1, a BMP type I receptor, in cerebrovascular endothelium. Subsequent activation of activin receptor-like kinase 1 enhances expression of Notch ligands Jagged 1 and 2, which increases Notch activity and alters the expression of Ephrin B2 and Ephrin receptor B4, arterial and venous endothelial markers, respectively. Reducing the expression of Jagged 1 and 2 in the Mgp(-/-) mice by crossing them with Jagged 1 or 2 deficient mice reduces Notch activity, normalizes endothelial differentiation, and prevents cerebral AVMs, but not pulmonary or renal AVMs. Our results suggest that Notch signaling mediates and can modulate changes in BMP signaling that lead to cerebral AVMs.
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