ArticleThe Journal of biological chemistry2010
Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 1 of them a synthesis that pooled it.
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
219 citing papers in PubMed, 1 synthesis or guideline pooled it, 424 citations in OpenAlex.
- SIRT3 as a potential biomarker and therapeutic target for cardiovascular diseases: a meta-analysis of clinical studies.Future cardiology · 2025Pooled it
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- TFAM promotes mitochondrial division by increasing mitochondrial Sirt3.Cell death & disease · 2026Article
- Cyclic tensile loading regulates nucleus pulposus cell autophagy through mitochondrial dynamics: molecular mechanisms and implications.Journal of translational medicine · 2026Review
- Nicotinamide adenine dinucleotide inhibits the production of reactive oxygen species and myocardial cell pyroptosis caused by hypoxia/re-oxygenation injury.World journal of cardiology · 2026Article
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- SIRT3/AMPK-Driven Mitophagy Failure Underlies Methylmercury-Induced Neurotoxicity: Evidence from Humans to Cells.Molecular neurobiology · 2025Article
- Review
- Nicotinamide Adenine Dinucleotide Supplementation to Alleviate Heart Failure: A Mitochondrial Dysfunction Perspective.Nutrients · 2025Review
- Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischaemic injury involves direct activation of mitochondrial sirtuin 3.Cardiovascular research · 2025Article
- Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics.Scientific reports · 2025Article
- Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.Cardiovascular drugs and therapy · 2024Article
- NAD metabolism and heart failure: Mechanisms and therapeutic potentials.Journal of molecular and cellular cardiology · 2024Review
- Deciphering metabolomics and lipidomics landscape in zebrafish hypertrophic cardiomyopathy model.Scientific reports · 2024Article
- The study on the role of O-GlcNAcylation of SIRT3 in regulating mitochondrial oxidative stress during simulate myocardial ischemia-reperfusion.Scientific reports · 2024Article
- Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- The Role of Mitochondrial Sirtuins (SIRT3, SIRT4 and SIRT5) in Renal Cell Metabolism: Implication for Kidney Diseases.International journal of molecular sciences · 2024Review
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Mitochondrial SIRT3 as a protective factor against cyclosporine A-induced nephrotoxicity.Scientific reports · 2024Article
- NAD in pathological cardiac remodeling: Metabolic regulation and beyond.Biochimica et biophysica acta. Molecular basis of disease · 2024Review
159 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
10 authors at 2 institutions in 1 country.
Funding
Abstract
Since the discovery of NAD-dependent deacetylases, sirtuins, it has been recognized that maintaining intracellular levels of NAD is crucial for the management of stress response of cells. Here we show that agonist-induced cardiac hypertrophy is associated with loss of intracellular levels of NAD, but not exercise-induced physiologic hypertrophy. Exogenous addition of NAD was capable of maintaining intracellular levels of NAD and blocking the agonist-induced cardiac hypertrophic response in vitro as well as in vivo. NAD treatment blocked the activation of pro-hypertrophic Akt1 signaling, and augmented the activity of anti-hypertrophic LKB1-AMPK signaling in the heart, which prevented subsequent induction of mTOR-mediated protein synthesis. By using gene knock-out and transgenic mouse models of SIRT3 and SIRT1, we showed that the anti-hypertrophic effects of exogenous NAD are mediated through activation of SIRT3, but not SIRT1. SIRT3 deacetylates and activates LKB1, thus augmenting the activity of the LKB1-AMPK pathway. These results reveal a novel role of NAD as an inhibitor of cardiac hypertrophic signaling, and suggest that prevention of NAD depletion may be critical in the treatment of cardiac hypertrophy and heart failure.
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.