ArticleCardiovascular research2021
Metformin directly suppresses atherosclerosis in normoglycaemic mice via haematopoietic adenosine monophosphate-activated protein kinase.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Monocytes as a convergent nanoparticle therapeutic target for cardiovascular diseases.Advanced drug delivery reviews · 2022Pooled it
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- Environmental modulators of vascular physiology and inflammation.Experimental physiology · 2026Review
- Identification of novel biomarkers for hypertension and ventricular remodeling based on transcriptomics and machine learning.iScience · 2025Article
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Dual modulation of atherosclerosis by exercise and metformin: convergent pathways, divergent outcomes, and therapeutic potential.Clinical hypertension · 2025Review
- Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.Immunity, inflammation and disease · 2024Review
- The Multifaceted Nature of Macrophages in Cardiovascular Disease.Biomedicines · 2024Review
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
- Two sides of the same coin: Non-alcoholic fatty liver disease and atherosclerosis.Vascular pharmacology · 2024Review
- Molecular mechanisms of action of metformin: latest advances and therapeutic implications.Clinical and experimental medicine · 2023Review
- The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials.Archives of pharmacal research · 2023Review
- Transcriptomic Establishment of Pig Macrophage Polarization Signatures.Current issues in molecular biology · 2023Article
- Macrophage Phenotyping in Atherosclerosis by Proteomics.International journal of molecular sciences · 2023Review
- Old drug, new tricks: the utility of metformin in infection and vaccination responses to influenza and SARS-CoV-2 in older adults.Frontiers in aging · 2023Review
- Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.Journal of cellular and molecular medicine · 2022Review
- Endothelial UCP2 Is a Mechanosensitive Suppressor of Atherosclerosis.Circulation research · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Metformin: Expanding the Scope of Application-Starting Earlier than Yesterday, Canceling Later.International journal of molecular sciences · 2022Review
- Lysosome (Dys)function in Atherosclerosis-A Big Weight on the Shoulders of a Small Organelle.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsAtherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque haemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and activating transcription factor 1 (ATF1). The antidiabetic drug metformin may also activate AMPK-dependent signalling. Hypothesis: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, thereby suppresses atherogenesis. METHODS AND
resultsNormoglycaemic Ldlr-/- hyperlipidaemic mice were treated with oral metformin, which profoundly suppressed atherosclerotic lesion development (P < 5 × 10-11). Bone marrow transplantation from AMPK-deficient mice demonstrated that metformin-related atheroprotection required haematopoietic AMPK [analysis of variance (ANOVA), P < 0.03]. Metformin at a clinically relevant concentration (10 μM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1, and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages. Similar effects were seen in human blood-derived macrophages, in which metformin-induced protective genes and M2-like genes, suppressible by si-ATF1-mediated knockdown. Microarray analysis comparing metformin with heme in human macrophages indicated that the transcriptomic effects of metformin were related to those of heme, but not identical. Metformin-induced lesional macrophage expression of p-AMPK, p-ATF1, and downstream M2-like protective effects.
conclusionMetformin activates a conserved AMPK-ATF1-M2-like pathway in mouse and human macrophages, and results in highly suppressed atherogenesis in hyperlipidaemic mice via haematopoietic AMPK.
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