ArticlePloS one2014
Sirtuin 1 (SIRT1) activation mediates sildenafil induced delayed cardioprotection against ischemia-reperfusion injury in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Pooled it
- A Meta-Analysis of Resveratrol Protects against Myocardial Ischemia/Reperfusion Injury: Evidence from Small Animal Studies and Insight into Molecular Mechanisms.Oxidative medicine and cellular longevity · 2019Pooled it
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Vardenafil Alleviates Doxorubicin-Induced Cardiotoxicity Associated with Restoration of the AMPK/SIRT1 Signaling Pathway.Biomedicines · 2026Article
- Review
- Review
- mPeerJ · 2023Article
- Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.Signal transduction and targeted therapy · 2022Review
- NOX4 stimulates ANF secretion via activation of the Sirt1/Nrf2/ATF3/4 axis in hypoxic beating rat atria.Molecular medicine reports · 2022Article
- A Comprehensive Analysis of the Efficacy of Resveratrol in Atherosclerotic Cardiovascular Disease, Myocardial Infarction and Heart Failure.Molecules (Basel, Switzerland) · 2021Review
- Critical role of SIRT1 upregulation on the protective effect of lncRNA ANRIL against hypoxia/reoxygenation injury in H9c2 cardiomyocytes.Molecular medicine reports · 2021Article
- SIRT1 alleviates hepatic ischemia-reperfusion injury via the miR-182-mediated XBP1/NLRP3 pathway.Molecular therapy. Nucleic acids · 2021Article
- Histone deacetylases in modulating cardiac disease and their clinical translational and therapeutic implications.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- NADSignal transduction and targeted therapy · 2020Review
- PDE5 inhibitor sildenafil attenuates cardiac microRNA 214 upregulation and pro-apoptotic signaling after chronic alcohol ingestion in mice.Molecular and cellular biochemistry · 2020Article
- Phosphodiesterase Inhibitors for Alzheimer's Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale.Journal of Alzheimer's disease reports · 2020Review
- Cardiac metabolism as a driver and therapeutic target of myocardial infarction.Journal of cellular and molecular medicine · 2020Review
- Sildenafil for the Treatment of Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease reports · 2020Review
- Biphasic Effect of Sildenafil on Energy Sensing is Mediated by Phosphodiesterases 2 and 3 in Adipocytes and Hepatocytes.International journal of molecular sciences · 2019Article
- Sirtuins and NADCirculation research · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIt has been well documented that phosphodiesterase-5 inhibitor, sildenafil (SIL) protects against myocardial ischemia/reperfusion (I-R) injury. SIRT1 is part of the class III Sirtuin family of histone deacetylases that deacetylates proteins involved in cellular stress response including those related to I-R injury. OBJECTIVE/HYPOTHESIS: We tested the hypothesis that SIL-induced cardioprotection may be mediated through activation of SIRT1.
methodsAdult male ICR mice were treated with SIL (0.7 mg/kg, i.p.), Resveratrol (RSV, 5 mg/kg, a putative activator of SIRT1 used as the positive control), or saline (0.2 mL). The hearts were harvested 24 hours later and homogenized for SIRT1 activity analysis.
resultsBoth SIL- and RSV-treated mice had increased cardiac SIRT1 activity (P<0.001) as compared to the saline-treated controls 24 hours after drug treatment. In isolated ventricular cardiomyocytes, pretreatment with SIL (1 µM) or RSV (1 µM) for one hour in vitro also upregulated SIRT1 activity (P<0.05). We further examined the causative relationship between SIRT1 activation and SIL-induced late cardioprotection. Pretreatment with SIL (or RSV) 24 hours prior to 30 min ischemia and 24 hours of reperfusion significantly reduced infarct size, which was associated with a significant increase in SIRT1 activity (P<0.05). Moreover, sirtinol (a SIRT1 inhibitor, 5 mg/kg, i.p.) given 30 min before I-R blunted the infarct-limiting effect of SIL and RSV (P<0.001).
conclusionOur study shows that activation of SIRT1 following SIL treatment plays an essential role in mediating the SIL-induced cardioprotection against I-R injury. This newly identified SIRT1-activating property of SIL may have enormous therapeutic implications.
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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.