Evidence map›Paper›PMID 25504881›Full record

ArticleScience translational medicine2014

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase.

Yan Liu, Aarti Asnani, Lin Zou, Victoria L Bentley, Min Yu, You Wang, Graham Dellaire, Kumar S Sarkar, Matthew Dai, Howard H Chen and 6 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
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

68 citing papers in PubMed, 135 citations in OpenAlex.

  1. Review
  2. MDH2 S246 phosphorylation protects mitochondria against hypoxia/reoxygenation injury due to acetate/lactate metabolism.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Article
  3. Article
  4. Review
  5. Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026
    Review
  6. Article
  7. Review
  8. Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Regulated cell death pathways in cardiomyopathy.Acta pharmacologica Sinica · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

8 more citing papers are in PubMed but not listed here.

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

16 authors at 6 institutions in 2 countries.

Yan LiuCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA.
Aarti AsnaniCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA.
Lin ZouDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Victoria L BentleyDepartment of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
Min YuMassachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.
You WangCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA.
Graham DellaireDepartment of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada. Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
Kumar S SarkarCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA.
Matthew DaiCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Howard H ChenCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
David E SosnovikCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Jordan T ShinCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Daniel A HaberMassachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute.
Jason N BermanDepartment of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada. Department of Pediatrics, Izaak Walton Killam Health Centre, Halifax, Nova Scotia B3K 6R8, Canada.
Wei ChaoDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Randall T PetersonCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA. rtpeterson@mgh.harvard.edu.
Broad Institute · USDalhousie University · CAHarvard University · USMassachusetts General Hospital · USAthinoula A. Martinos Center for Biomedical Imaging · USHoward Hughes Medical Institute · US

Funding

MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
Multiplexed Molecular Imaging of Cell Death PathwaysK99HL121152 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, HOWARD H. · 2014 to 2015
$298k
CIHRHoward Hughes Medical InstituteNHLBI NIH HHS K99 HL121152NHLBI NIH HHS T32 HL007208NHLBI NIH HHS T32HL007208
6 · The paper itself

Abstract

Doxorubicin is a highly effective anticancer chemotherapy agent, but its use is limited by its cardiotoxicity. To develop a drug that prevents this toxicity, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulates the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and found that visnagin (VIS) and diphenylurea (DPU) rescue the cardiac performance and circulatory defects caused by doxorubicin in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. VIS treatment improved cardiac contractility in doxorubicin-treated mice. Further, VIS and DPU did not reduce the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we found that VIS binds to mitochondrial malate dehydrogenase (MDH2), a key enzyme in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS' cardioprotective effects. Thus, VIS and DPU are potent cardioprotective compounds, and MDH2 is a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCarbanilidesCardiomyopathiesCardiotonic AgentsCell Line, TumorDoxorubicinHeartHumansKhellinMalate DehydrogenaseMaleMiceMice, Inbred C57BLMitochondriaAntineoplastic AgentsCarbanilidesCardiotonic AgentsDoxorubicinKhellinMalate Dehydrogenasevisnagin

Identifiers

PMID25504881
PMCPMC4360984
OpenAlexW2038973948

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.