Evidence mapPaperPMID 40606000Full record

ArticleDrug design, development and therapy2025

Cardioprotection Through Pharmacological Activation of Sirtuin 5 in a Murine Model of Acute Myocardial Infarction.

Carola Castiello, Panagiotis Efentakis, Panagiota-Efstathia Nikolaou, Lydia Symeonidi, Christina Chania, Ioanna Barla, Ifigeneia Akrani, Nikolaos Kostomitsopoulos, Evangelos Gikas, Nikolaos S Thomaidis and 7 more

Abstract read
In one paragraph

Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Carola CastielloLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Panagiotis EfentakisLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Panagiota-Efstathia NikolaouLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Lydia SymeonidiLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Christina ChaniaLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.ORCID 0000-0002-3396-7993
Ioanna BarlaSchool of Chemistry, National and Kapodistrian University of Athens, Athens, 15772, Greece.
Ifigeneia AkraniDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Nikolaos KostomitsopoulosBiomedical Research Foundation of the Academy of Athens, Athens, 11527, Greece.
Evangelos GikasSchool of Chemistry, National and Kapodistrian University of Athens, Athens, 15772, Greece.
Nikolaos S ThomaidisSchool of Chemistry, National and Kapodistrian University of Athens, Athens, 15772, Greece.
Emmanuel MikrosDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
Petra KleinbongardInstitute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Essen, 45122, Germany.
Rossella FioravantiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, 00185, Italy.
Clemens ZwergelDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, 00185, Italy.ORCID 0000-0002-3097-0003
Sergio ValenteDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, 00185, Italy.
Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, 00185, Italy.ORCID 0000-0001-9176-2382
Ioanna AndreadouLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Sirtuins (SIRTs) play a critical role in redox and metabolic regulation of the myocardium; however, the cardioprotective potential of SIRT5 in terms of infarct size (IS) reduction is still elusive. Herein, we employed the newly synthesized SIRT5-specific agonist, MC3215, developed by our group, to explore for the first time the pharmacological activation of SIRT5 as a target for cardioprotection. Methods and Results: In in vitro screening experiments, SIRT1 and SIRT5 agonists, namely, MC2606 and MC3215, at 1-20 μΜ were added to cardiomyoblasts (H9c2) and human endothelial cells (EA.hy-926) during 24 h hypoxia/2 h reoxygenation (H/R). SIRT1 and SIRT5 agonists mitigated H/R injury. Male C57BL/6J mice underwent 30 min ischemia (I) followed by 2 h or 24 h reperfusion (R). Mice received vehicle, the SIRT1 or SIRT5 agonists at 20 and 30 mg/kg at the 20th min of ischemia, and IS was quantified via triphenyl-tetrazolium chloride staining (n=5-7/group). MC3215-mediated SIRT5 activation reduced IS at 24 h R at 20mg/kg compared to controls (25.18±2.7% vs 38.80±4.7%). MC3215 treatment resulted in reduced protein malonylation in all experimental settings. Targeted mass-spectrometry-based metabolomics in the ischemic heart at the 10 Conclusion: SIRT5 pharmacological agonism emerges as a novel cardioprotective target, leading to RISK pathway activation and mitochondria-related metabolic effects, converging at salvaging ischemic myocardium from I/R injury.

Indexed as

Cardiotonic AgentsDisease Models, AnimalMyocardial InfarctionSirtuinsAnimalsDose-Response Relationship, DrugHumansMaleMiceMice, Inbred C57BLMolecular StructureMyocardial Reperfusion InjuryRatsSirtuin 1Structure-Activity RelationshipCardiotonic AgentsSIRT5 protein, humanSIRT5 protein, mouseSirtuin 1Sirtuinscardioprotectionmyocardial ischemia/reperfusion injurySIRT5sirtuins

Identifiers

PMID40606000
PMCPMC12214431

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.