ArticleJournal of neuroinflammation2020
Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06405971 (Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms: a Prospective, Randomized Study (METTLE)
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Associations Between Drug Treatments and the Risk of Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-analysis.Translational stroke research · 2023Pooled it
- Intracranial aneurysms as a manifestation of premature vascular aging: Cellular senescence, inflammaging, and wall degeneration.Ageing research reviews · 2026Review
- CHI3L1: a novel regulator of vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Effect of Metformin in Diabetic Patients After Treatment of Intracranial Aneurysm: A Nationwide Cohort Study.Journal of Korean medical science · 2026Article
- SPARC modulates macrophage-like phenotype transformation in VSMCs and triggers a vicious cycle.Frontiers in cell and developmental biology · 2026Article
- Silencing MALAT1 represses pathological progression, inflammation, and vascular smooth muscle cell phenotype switching by regulating the SEMA3C-mediated Smad pathway in intracranial aneurysms.Frontiers in cellular neuroscience · 2026Article
- Article
- METTL3 promotes vascular stability in intracranial aneurysm via m6A-AMPK axis.Scientific reports · 2025Article
- Time to Consider Pharmacologic Management of Unruptured Intracranial Aneurysms?Journal of stroke · 2025Review
- Multiomics reveals metformin's dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention.Scientific reports · 2025Article
- Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population.Journal of stroke · 2025Article
- Regulation of vascular smooth muscle cells phenotype by metformin up-regulated miR-1/ CCND1 axis via targeting AMPK/TGF-β signaling pathway.Molecular biology reports · 2025Article
- GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence.Neurosurgical review · 2025Article
- ERBB4 as a therapeutic target in aortic dissection: Implications for cell-based therapies in vascular regeneration.Biomolecules & biomedicine · 2025Article
- Comprehensive analysis the role of cuproptosis related genes in abdominal aortic aneurysm.Annals of medicine and surgery (2012) · 2025Article
- Animal Models of Intracranial Aneurysms: History, Advances, and Future Perspectives.Translational stroke research · 2025Review
- The Role of miRNAs in Aneurysmal Subarachnoid Hemorrhage.Current molecular medicine · 2025Review
- Pharmaceutical Modulation of Intracranial Aneurysm Development and Rupture.Journal of clinical medicine · 2024Review
- Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in intracranial aneurysms.Non-coding RNA research · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe regulation of vascular smooth muscle cell (VSMC) phenotype plays an important role in intracranial aneurysm (IA) formation and progression. However, the underlying mechanism remains unclear. Metformin is a 5' AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature. The present study investigated whether metformin modulates VSMC phenotype switching via the AMPK/acetyl-CoA carboxylase (ACC) pathway during IA pathogenesis.
methodsAdult male Sprague-Dawley rats (n = 80) were used to establish an elastase-induced IA model. The effects of metformin on AMPK activation and VSMC phenotype modulation were examined. We also established a platelet-derived growth factor (PDGF)-BB-induced VSMC model and analyzed changes in phenotype including proliferation, migration, and apoptosis as well as AMPK/ACC axis activation under different doses of metformin, AMPK antagonist, ACC antagonist, and their combinations.
resultsMetformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines. AMPK/ACC axis activation inhibited the proliferation, migration, and apoptosis of VSMCs, in which phenotypic switching was induced by PDGF-BB.
conclusionsMetformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA.
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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.