Evidence map›Paper›PMID 37397084›Full record

ArticleJACC. CardioOncology2023

Evaluation of Senescence and Its Prevention in Doxorubicin-Induced Cardiotoxicity Using Dynamic Engineered Heart Tissues.

Annet N Linders, Itamar B Dias, Ekaterina S Ovchinnikova, Mathilde C S C Vermeer, Martijn F Hoes, George Markousis Mavrogenis, Frederik E Deiman, Karla F Arevalo Gomez, Jacqueline M Bliley, Jamil Nehme and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. CardioOncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Review
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  10. How to measure and model cardiovascular aging.Cardiovascular research · 2025
    Review
  11. Article
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  14. Review
  15. Article
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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

21 authors.

Annet N LindersDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Itamar B DiasDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Ekaterina S OvchinnikovaDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Mathilde C S C VermeerDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Martijn F HoesDepartment of Clinical Genetics, Maastricht University Medical Center+, Maastricht, the Netherlands.
George Markousis MavrogenisDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Frederik E DeimanDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Karla F Arevalo GomezDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Jacqueline M BlileyRegenerative Biomaterials and Therapeutics Group, Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania.
Jamil NehmeEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Aryan VinkDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Jourik GietemaDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Rudolf A de BoerDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Daan WestenbrinkDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Herman H W SilljeDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Denise Hilfiker-KleinerInstitute of Cardiovascular Complications in Pregnancy and in Oncologic Therapies, Philipps-Universität Marburg, Marburg, Germany.
Linda W van LaakeDivision of Heart and Lungs and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Adam W FeinbergRegenerative Biomaterials and Therapeutics Group, Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania.
Marco DemariaEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Nils BomerDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Peter van der MeerDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Doxorubicin is an essential cancer treatment, but its usefulness is hampered by the occurrence of cardiotoxicity. Nevertheless, the pathophysiology underlying doxorubicin-induced cardiotoxicity and the respective molecular mechanisms are poorly understood. Recent studies have suggested involvement of cellular senescence. Objectives: The aims of this study were to establish whether senescence is present in patients with doxorubicin-induced cardiotoxicity and to investigate if this could be used as a potential treatment target. Methods: Biopsies from the left ventricles of patients with severe doxorubicin-induced cardiotoxicity were compared with control samples. Additionally, senescence-associated mechanisms were characterized in 3-dimensional dynamic engineered heart tissues (dyn-EHTs) and human pluripotent stem cell-derived cardiomyocytes. These were exposed to multiple, clinically relevant doses of doxorubicin to recapitulate patient treatment regimens. To prevent senescence, dyn-EHTs were cotreated with the senomorphic drugs 5-aminoimidazole-4-carboxamide ribonucleotide and resveratrol. Results: Senescence-related markers were significantly up-regulated in the left ventricles of patients with doxorubicin-induced cardiotoxicity. Treatment of dyn-EHTs resulted in up-regulation of similar senescence markers as seen in the patients, accompanied by tissue dilatation, decreased force generation, and increased troponin release. Treatment with senomorphic drugs led to decreased expression of senescence-associated markers, but this was not accompanied by improved function. Conclusions: Senescence was observed in the hearts of patients with severe doxorubicin-induced cardiotoxicity, and this phenotype can be modeled in vitro by exposing dyn-EHTs to repeated clinically relevant doses of doxorubicin. The senomorphic drugs 5-aminoimidazole-4-carboxamide ribonucleotide and resveratrol prevent senescence but do not result in functional improvements. These findings suggest that preventing senescence by using a senomorphic during doxorubicin administration might not prevent cardiotoxicity.

Indexed as

cardiotoxicitydoxorubicinhPSC-derived cardiomyocytessenescencesenomorphic drugs

Identifiers

PMID37397084
PMCPMC10308053

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Registered trials

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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.