ArticleThe Journal of clinical investigation2012
Creatine kinase-mediated improvement of function in failing mouse hearts provides causal evidence the failing heart is energy starved.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 139 citations in OpenAlex.
- Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study.Cardiovascular diabetology · 2021 · on this mapTrial
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Article
- Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2025Article
- Article
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
- A Mitochondrial Basis for Heart Failure Progression.Cardiovascular drugs and therapy · 2024Review
- 25-Hydroxycholecalciferol Improves Cardiac Metabolic Adaption, Mitochondrial Biogenetics, and Redox Status to Ameliorate Pathological Remodeling and Functional Failure in Obese Chickens.Antioxidants (Basel, Switzerland) · 2024Article
- Maintaining energy provision in the heart: the creatine kinase system in ischaemia-reperfusion injury and chronic heart failure.Clinical science (London, England : 1979) · 2024Review
- Underlying mechanisms of ketotherapy in heart failure: current evidence for clinical implementations.Frontiers in pharmacology · 2024Review
- SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism.Nature reviews. Cardiology · 2023Review
- Contribution of skeletal muscle-specific microRNA-133b to insulin resistance in heart failure.American journal of physiology. Heart and circulatory physiology · 2023Article
- Influence of Isolated Resistance Exercise on Cardiac Remodeling, Myocardial Oxidative Stress, and Metabolism in Infarcted Rats.Antioxidants (Basel, Switzerland) · 2023Article
- CardiacHeart failure reviews · 2023Review
- Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolutionJournal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2023Article
- Article
- Ontogeny of cardiomyocytes: ultrastructure optimization to meet the demand for tight communication in excitation-contraction coupling and energy transfer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Creatine deficiency and heart failure.Heart failure reviews · 2022Review
- Myocardial ATP depletion detected noninvasively predicts sudden cardiac death risk in patients with heart failure.JCI insight · 2022Observational
- Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.Circulation research · 2022Observational
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
ATP is required for normal cardiac contractile function, and it has long been hypothesized that reduced energy delivery contributes to the contractile dysfunction of heart failure (HF). Despite experimental and clinical HF data showing reduced metabolism through cardiac creatine kinase (CK), the major myocardial energy reserve and temporal ATP buffer, a causal relationship between reduced ATP-CK metabolism and contractile dysfunction in HF has never been demonstrated. Here, we generated mice conditionally overexpressing the myofibrillar isoform of CK (CK-M) to test the hypothesis that augmenting impaired CK-related energy metabolism improves contractile function in HF. CK-M overexpression significantly increased ATP flux through CK ex vivo and in vivo but did not alter contractile function in normal mice. It also led to significantly increased contractile function at baseline and during adrenergic stimulation and increased survival after thoracic aortic constriction (TAC) surgery-induced HF. Withdrawal of CK-M overexpression after TAC resulted in a significant decline in contractile function as compared with animals in which CK-M overexpression was maintained. These observations provide direct evidence that the failing heart is "energy starved" as it relates to CK. In addition, these data identify CK as a promising therapeutic target for preventing and treating HF and possibly diseases involving energy-dependent dysfunction in other organs with temporally varying energy demands.
Indexed as
Identifiers
What OpenQuestion holds
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.