ArticleBiology of sex differences2021
Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.
Article in Biology of sex differences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Exploring the effects of moxibustion on pathological remodeling in rats with myocardial ischemia-reperfusion injury based on mitochondrial cardiolipin protection.Frontiers in pharmacology · 2026Article
- Sex-specific benefits of a combined supplementation of B vitamins, nicotinamide riboside, folate and cobalamin, in a murine model of heart failure.Biology of sex differences · 2025Article
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Novel Molecules Targeting Metabolism and Mitochondrial Function in Cardiac Diseases.Current cardiology reviews · 2025Review
- Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.Cardiovascular drugs and therapy · 2024Article
- A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis.Communications biology · 2024Article
- ALCAT1-mediated abnormal cardiolipin remodelling promotes mitochondrial injury in podocytes in diabetic kidney disease.Cell communication and signaling : CCS · 2024Article
- Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and mouse.PloS one · 2023Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects.
methodsTo decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice. This allowed us to avoid the eventual impact of AMPK-KO in peripheral organs.
resultsCardio-specific Ampkα2 deficiency led to a progressive left ventricular systolic dysfunction and the development of cardiac fibrosis in males. We observed a reduction in complex I-driven respiration without change in mitochondrial mass or in vitro complex I activity, associated with a rearrangement of the cardiolipins and reduced integration of complex I into the electron transport chain supercomplexes. Strikingly, none of these defects were present in females. Interestingly, suppression of estradiol signaling by ovariectomy partially mimicked the male sensitivity to AMPK loss, notably the cardiac fibrosis and the rearrangement of cardiolipins, but not the cardiac function that remained protected.
conclusionOur results confirm the close link between AMPK and cardiac mitochondrial function, but also highlight links with cardiac fibrosis. Importantly, we show that AMPK is differently involved in these processes in males and females, which may have clinical implications for the use of AMPK activators in the treatment of heart failure.
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