ArticleThe Journal of clinical investigation2009
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 573 papers, 2 of them syntheses 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
573 citing papers in PubMed, 2 syntheses or guidelines pooled it, 982 citations in OpenAlex.
- SIRT3 as a potential biomarker and therapeutic target for cardiovascular diseases: a meta-analysis of clinical studies.Future cardiology · 2025Pooled it
- Sirtuins in intervertebral disc degeneration: current understanding.Molecular medicine (Cambridge, Mass.) · 2024Pooled it
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- Targeting FOXO3 for the Management of Heart Failure: Current Evidence and Future Directions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Subcellular sirtuin signaling networks: pivotal regulators of cardiovascular homeostasis and remodeling.Journal of molecular histology · 2026Review
- SIRT3-dependent mitochondrial redox homeostasis protects against age-related tendon degeneration.Bone & joint research · 2026Article
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- The Plant Growth Regulator Forchlorfenuron (KT-30) Drives Atherosclerosis Progression via Lipid Homeostasis Disruption: Evidence from ApoE-Deficient Mice.Antioxidants (Basel, Switzerland) · 2026Article
- Advances in the Role of SIRT3 in Vascular Remodeling in Hypertension.Biomolecules · 2026Review
- Apigenin Protects Against Cisplatin-Induced Cardiotoxicity: Potential Involvement of CD38-Sirt3 Signaling in Rats.Molecules (Basel, Switzerland) · 2026Article
- Sirtuins at the Interface of Glucose Metabolism, Diabetes, and Heart Failure: Metabolic Sensing in Cardiometabolic Disease.International journal of molecular sciences · 2026Review
- Molecular Hydrogen as a Regulator of Mitochondrial Quality Control and Metabolic Reprogramming.International journal of molecular sciences · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Bioinformatics Identification and Molecular Docking Validation of Post-Translational Modification-Related Hub Genes as Diagnostic Biomarkers and Therapeutic Targets in Myocardial Fibrosis.International journal of molecular sciences · 2026Article
- Circadian rhythm disruption impairs ovarian follicular development via NADEBioMedicine · 2026Article
- Sirtuins mediate the reduction of age-related oxidative damage in the cochlea under a cocoa-rich diet.GeroScience · 2026Article
- Qishen Yiqi Dropping Pills Protect Against Myocardial Infarction in Mice via Activating SIRT3/FOXO3a Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Zinc Alleviates Oxidative Stress Injury of the Testis Induced by Zearalenone through Sirt3-Foxo3 Pathway in Mice.Biological trace element research · 2026Article
- Thymoquinone Protects Against Cardiac Hypertrophy via PPAR-γ/PI3K/Akt Pathway.Journal of cellular and molecular medicine · 2026Article
- MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
513 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased expression of SIRT3 has been linked to an extended life span in humans. Here, we have shown that Sirt3 protects the mouse heart by blocking the cardiac hypertrophic response. Although Sirt3-deficient mice appeared to have normal activity, they showed signs of cardiac hypertrophy and interstitial fibrosis at 8 weeks of age. Application of hypertrophic stimuli to these mice produced a severe cardiac hypertrophic response, whereas Sirt3-expressing Tg mice were protected from similar stimuli. In primary cultures of cardiomyocytes, Sirt3 blocked cardiac hypertrophy by activating the forkhead box O3a-dependent (Foxo3a-dependent), antioxidant-encoding genes manganese superoxide dismutase (MnSOD) and catalase (Cat), thereby decreasing cellular levels of ROS. Reduced ROS levels suppressed Ras activation and downstream signaling through the MAPK/ERK and PI3K/Akt pathways. This resulted in repressed activity of transcription factors, specifically GATA4 and NFAT, and translation factors, specifically eukaryotic initiation factor 4E (elf4E) and S6 ribosomal protein (S6P), which are involved in the development of cardiac hypertrophy. These results demonstrate that SIRT3 is an endogenous negative regulator of cardiac hypertrophy, which protects hearts by suppressing cellular levels of ROS.
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.