ArticleEMBO molecular medicine2012
Hexokinase II knockdown results in exaggerated cardiac hypertrophy via increased ROS production.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Metabolic Remodeling in the Pressure-Loaded Right Ventricle: Shifts in Glucose and Fatty Acid Metabolism-A Systematic Review and Meta-Analysis.Journal of the American Heart Association · 2019Pooled it
- Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy (HALT-HCM): A Randomized, Placebo-Controlled, Double-Blind Pilot Study.Circulation research · 2018Trial
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- ULK1 activates NCOA4‑mediated ferritinophagy via the Beclin1/VPS34 complex in cardiomyocyte hypertrophy.Molecular medicine reports · 2026Article
- Growth Phase-Dependent Changes in the Carbohydrate Metabolism of Penicillium Strains from Diverse Temperature Classes in Response to Cold Stress.International journal of molecular sciences · 2025Article
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- Article
- Hexokinase 2 expression in apical enterocytes correlates with inflammation severity in patients with inflammatory bowel disease.BMC medicine · 2024Article
- Landscape of glycolytic metabolites and their regulating proteins in myocardium from human heart failure with preserved ejection fraction.European journal of heart failure · 2024Article
- ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence.Autophagy · 2024Article
- Article
- Real-time resolution studies of the regulation of lactate production by hexokinases binding to mitochondria in single cells.PloS one · 2024Article
- Metabolic adaptations in pressure overload hypertrophic heart.Heart failure reviews · 2024Review
- DNA Damage and Nuclear Morphological Changes in Cardiac Hypertrophy Are Mediated by SNRK Through Actin Depolymerization.Circulation · 2023Article
- 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
- DNA damage and nuclear morphological changes in cardiac hypertrophy are mediated by SNRK through actin depolymerization.bioRxiv : the preprint server for biology · 2023Article
- Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hexokinase-II (HKII) is highly expressed in the heart and can bind to the mitochondrial outer membrane. Since cardiac hypertrophy is associated with a substrate switch from fatty acid to glucose, we hypothesized that a reduction in HKII would decrease cardiac hypertrophy after pressure overload. Contrary to our hypothesis, heterozygous HKII-deficient (HKII(+/-)) mice displayed increased hypertrophy and fibrosis in response to pressure overload. The mechanism behind this phenomenon involves increased levels of reactive oxygen species (ROS), as HKII knockdown increased ROS accumulation, and treatment with the antioxidant N-acetylcysteine (NAC) abrogated the exaggerated response. HKII mitochondrial binding is also important for the hypertrophic effects, as HKII dissociation from the mitochondria resulted in de novo hypertrophy, which was also attenuated by NAC. Further studies showed that the increase in ROS levels in response to HKII knockdown or mitochondrial dissociation is mediated through increased mitochondrial permeability and not by a significant change in antioxidant defenses. Overall, these data suggest that HKII and its mitochondrial binding negatively regulate cardiac hypertrophy by decreasing ROS production via mitochondrial permeability.
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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.