ArticleHuman molecular genetics2016
Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- When and why is surgical revascularization indicated for the treatment of moyamoya syndrome in patients with RASopathies? A systematic review of the literature and a single institute experience.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Pooled it
- Aorto-Renal Dysplasia in Childhood: The Overlap of Neurofibromatosis Type 1 and Pediatric Renovascular Hypertension.Current hypertension reports · 2026Review
- Neurovascular Issues in Neurofibromatosis Type I: Focus on Intracranial Stenosis.Life (Basel, Switzerland) · 2026Review
- Loss of neurofibromin induces inflammatory macrophage phenotypic switch and retinal neovascularization via GLUT1 activation.Cell reports · 2025Article
- The Nf1-Q181X point mutation induces M2 macrophage polarization via the AKT/STAT pathway to promote smooth muscle cell proliferation and migration.Molecular biology reports · 2024Article
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- The Q181X Point Mutation in Nf1 Induces Cerebral Vessel Stenosis.Neuroscience bulletin · 2023Article
- The role of monocytes in thrombotic diseases: a review.Frontiers in cardiovascular medicine · 2023Review
- An update on the central nervous system manifestations of neurofibromatosis type 1.Acta neuropathologica · 2020Review
- Emerging therapeutic targets for neurofibromatosis type 1.Expert opinion on therapeutic targets · 2018Review
- Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization.Investigative ophthalmology & visual science · 2018Article
- A novel interaction between CXJournal of neuroinflammation · 2018Article
- Genetic and Epigenetic Regulation of Aortic Aneurysms.BioMed research international · 2017Review
- Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans.Free radical biology & medicine · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Persons with neurofibromatosis type 1 (NF1) have a predisposition for premature and severe arterial stenosis. Mutations in the NF1 gene result in decreased expression of neurofibromin, a negative regulator of p21(Ras), and increases Ras signaling. Heterozygous Nf1 (Nf1(+/-)) mice develop a marked arterial stenosis characterized by proliferating smooth muscle cells (SMCs) and a predominance of infiltrating macrophages, which closely resembles arterial lesions from NF1 patients. Interestingly, lineage-restricted inactivation of a single Nf1 allele in monocytes/macrophages is sufficient to recapitulate the phenotype observed in Nf1(+/-) mice and to mobilize proinflammatory CCR2+ monocytes into the peripheral blood. Therefore, we hypothesized that CCR2 receptor activation by its primary ligand monocyte chemotactic protein-1 (MCP-1) is critical for monocyte infiltration into the arterial wall and neointima formation in Nf1(+/-) mice. MCP-1 induces a dose-responsive increase in Nf1(+/-) macrophage migration and proliferation that corresponds with activation of multiple Ras kinases. In addition, Nf1(+/-) SMCs, which express CCR2, demonstrate an enhanced proliferative response to MCP-1 when compared with WT SMCs. To interrogate the role of CCR2 activation on Nf1(+/-) neointima formation, we induced neointima formation by carotid artery ligation in Nf1(+/-) and WT mice with genetic deletion of either MCP1 or CCR2. Loss of MCP-1 or CCR2 expression effectively inhibited Nf1(+/-) neointima formation and reduced macrophage content in the arterial wall. Finally, administration of a CCR2 antagonist significantly reduced Nf1(+/-) neointima formation. These studies identify MCP-1 as a potent chemokine for Nf1(+/-) monocytes/macrophages and CCR2 as a viable therapeutic target for NF1 arterial stenosis.
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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.