ArticleCirculation research2011
Reduction in hexokinase II levels results in decreased cardiac function and altered remodeling after ischemia/reperfusion injury.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 89 citations in OpenAlex.
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Biological Actions of Alamandine: A Scoping Review.Biomedicines · 2025Review
- ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.Communications biology · 2025Article
- Cardiac Regeneration in Adult Zebrafish: A Review of Signaling and Metabolic Coordination.Current cardiology reports · 2025Review
- MTX2 facilitates PKM2 tetramerization to promote cardiac glucose metabolism and protects the heart against ischemia/reperfusion injury.Theranostics · 2025Article
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- Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury.Nature aging · 2024Article
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.Basic research in cardiology · 2023Review
- Transcriptomic profiling of mare endometrium at different stages of endometrosis.Scientific reports · 2023Article
- Article
- Upregulation of glycolytic enzyme PFKFB3 by deubiquitinase OTUD4 promotes cardiac fibrosis post myocardial infarction.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart.International journal of molecular sciences · 2022Review
- Review
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications.Journal of clinical medicine · 2021Review
- Lactate and Myocardiac Energy Metabolism.Frontiers in physiology · 2021Review
- The Role of Metabolism in Heart Failure and Regeneration.Frontiers in cardiovascular medicine · 2021Review
- Cardiac metabolism as a driver and therapeutic target of myocardial infarction.Journal of cellular and molecular medicine · 2020Review
- Forced expression of miR-143 and -145 in cardiomyocytes induces cardiomyopathy with a reductive redox shift.Cellular & molecular biology letters · 2020Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
rationaleCardiomyocytes switch substrate utilization from fatty acid to glucose under ischemic conditions; however, it is unknown how perturbations in glycolytic enzymes affect cardiac response to ischemia/reperfusion (I/R). Hexokinase (HK)II is a HK isoform that is expressed in the heart and can bind to the mitochondrial outer membrane.
objectiveWe sought to define how HKII and its binding to mitochondria play a role in cardiac response and remodeling after I/R. METHODS AND
resultsWe first showed that HKII levels and its binding to mitochondria are reduced 2 days after I/R. We then subjected the hearts of wild-type and heterozygote HKII knockout (HKII(+/)⁻) mice to I/R by coronary ligation. At baseline, HKII(+/)⁻ mice have normal cardiac function; however, they display lower systolic function after I/R compared to wild-type animals. The mechanism appears to be through an increase in cardiomyocyte death and fibrosis and a reduction in angiogenesis; the latter is through a decrease in hypoxia-inducible factor-dependent pathway signaling in cardiomyocytes. HKII mitochondrial binding is also critical for cardiomyocyte survival, because its displacement in tissue culture with a synthetic peptide increases cell death. Our results also suggest that HKII may be important for the remodeling of the viable cardiac tissue because its modulation in vitro alters cellular energy levels, O₂ consumption, and contractility.
conclusionsThese results suggest that reduction in HKII levels causes altered remodeling of the heart in I/R by increasing cell death and fibrosis and reducing angiogenesis and that mitochondrial binding is needed for protection of cardiomyocytes.
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