ArticleHypertension (Dallas, Tex. : 1979)2014
Metformin protects against systolic overload-induced heart failure independent of AMP-activated protein kinase α2.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 79 citations in OpenAlex.
- Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status.Circulation research · 2016Trial
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- The impact of metformin on myocardial hypertrophy: an updated systematic review, meta-analysis, and meta-regression of randomized controlled trials.Diabetology & metabolic syndrome · 2025Review
- The Role of AMPKα in the Mechanism of Development and Treatment of Heart Failure.Reviews in cardiovascular medicine · 2025Review
- Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- Cell cycle arrest of cardiomyocytes in the context of cardiac regeneration.Frontiers in cardiovascular medicine · 2025Review
- New concepts in the roles of AMPK in adipocyte stem cell biology.Essays in biochemistry · 2024Review
- Resveratrol Inhibits Zinc Deficiency-Induced Mitophagy and Exerts Cardiac Cytoprotective Effects.Biological trace element research · 2024Article
- Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK.American journal of physiology. Heart and circulatory physiology · 2023Article
- Metformin preconditioning protects against myocardial stunning and preserves protein translation in a mouse model of cardiac arrest.Journal of molecular and cellular cardiology plus · 2023Article
- Metformin Inhibits Autophagy, Mitophagy and Antagonizes Doxorubicin-Induced Cardiomyocyte Death.International journal of drug discovery and pharmacology · 2023Article
- Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.Journal of cellular and molecular medicine · 2022Review
- Rhein attenuates angiotensin II-induced cardiac remodeling by modulating AMPK-FGF23 signaling.Journal of translational medicine · 2022Article
- Cardiac Hypertrophy: From Pathophysiological Mechanisms to Heart Failure Development.Reviews in cardiovascular medicine · 2022Review
- Small molecule QF84139 ameliorates cardiac hypertrophy via activating the AMPK signaling pathway.Acta pharmacologica Sinica · 2022Article
- Demystifying the Relationship Between Metformin, AMPK, and Doxorubicin Cardiotoxicity.Frontiers in cardiovascular medicine · 2022Review
- Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence.Biomolecules · 2021Review
- Autophagy in cardiovascular diseases: role of noncoding RNAs.Molecular therapy. Nucleic acids · 2021Review
- Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients.Life (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of AMP-activated protein kinase (AMPK)-α2 protects the heart against pressure overload-induced heart failure in mice. Although metformin is a known activator of AMPK, it is unclear whether its cardioprotection acts independently of an AMPKα2-dependent pathway. Because the role of AMPKα1 stimulation on remodeling of failing hearts is poorly defined, we first studied the effects of disruption of both the AMPKα1 and AMPKα2 genes on the response to transverse aortic constriction-induced left ventricular (LV) hypertrophy and dysfunction in mice. AMPKα2 gene knockout significantly exacerbated the degree of transverse aortic constriction-induced LV hypertrophy and dysfunction, whereas AMPKα1 gene knockout had no effect on the degree of transverse aortic constriction-induced LV hypertrophy and dysfunction. Administration of metformin was equally effective in attenuating transverse aortic constriction-induced LV remodeling in both wild-type and AMPKα2 knockout mice, as evidenced by reduced LV and lung weights, a preserved LV ejection fraction, and reduced phosphorylation of mammalian target of rapamycin (p-mTOR(Ser2448)) and its downstream target p-p70S6K(Thr389). These data support the notion that activation of AMPKα1 plays a negligible role in protecting the heart against the adverse effects of chronic pressure overload, and that metformin protects against adverse remodeling through a pathway that seems independent of AMPKα2.
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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.