Evidence map›Paper›PMID 34396166›Full record

ArticleJACC. CardioOncology2019

Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection.

Adeline Gasser, Yu-Wen Chen, Anais Audebrand, Ayhan Daglayan, Marine Charavin, Brigitte Escoubet, Pavel Karpov, Igor Tetko, Michael W Y Chan, Daniela Cardinale and 2 more

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

Article in JACC. CardioOncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Cardiotoxicity of Anthracyclines.Frontiers in cardiovascular medicine · 2020
    Review
  10. Article
  11. 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

12 authors at 6 institutions in 4 countries.

Adeline GasserLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Yu-Wen ChenInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Anais AudebrandLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Ayhan DaglayanLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Marine CharavinLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Brigitte EscoubetFRIM UMS37, Hospital Bichat assistance public-Paris Hospital, University of Paris Diderot, PRES Paris Cité, DHU FIRE, Inserm U1138, Paris, France.
Pavel KarpovInstitute of Structural Biology, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Igor TetkoInstitute of Structural Biology, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Michael W Y ChanDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Daniela CardinaleCardioncology Unit, European Institute of Oncology, I.R.C.C.S., Milan Italy.
Laurent DésaubryLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Canan G NebigilLaboratory of Cardio-Oncology and Medicinal Chemistry, CNRS (FRE2033), Illkirch, France.
Centre National de la Recherche Scientifique · FRHelmholtz Zentrum München · DEEuropean Institute of Oncology · ITInserm · FRInstitute of Biomedical Sciences, Academia Sinica · TWNational Chung Cheng University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThis study investigated how different concentrations of doxorubicin (DOX) can affect the function of cardiac cells. This study also examined whether activation of prokineticin receptor (PKR)-1 by a nonpeptide agonist, IS20, prevents DOX-induced cardiovascular toxicity in mouse models.

backgroundHigh prevalence of heart failure during and following cancer treatments remains a subject of intense research and therapeutic interest.

methodsThis study used cultured cardiomyocytes, endothelial cells (ECs), and epicardium-derived progenitor cells (EDPCs) for in vitro assays, tumor-bearing models, and acute and chronic toxicity mouse models for in vivo assays

resultsBrief exposure to cardiomyocytes with high-dose DOX increased the accumulation of reactive oxygen species (ROS) by inhibiting a detoxification mechanism via stabilization of cytoplasmic nuclear factor, erythroid 2. Prolonged exposure to medium-dose DOX induced apoptosis in cardiomyocytes, ECs, and EDPCs. However, low-dose DOX promoted functional defects without inducing apoptosis in EDPCs and ECs. IS20 alleviated detrimental effects of DOX in cardiac cells by activating the serin threonin protein kinase B (Akt) or mitogen-activated protein kinase pathways. Genetic or pharmacological inactivation of PKR1 subdues these effects of IS20. In a chronic mouse model of DOX cardiotoxicity, IS20 normalized an elevated serum marker of cardiotoxicity and vascular and EDPC deficits, attenuated apoptosis and fibrosis, and improved the survival rate and cardiac function. IS20 did not interfere with the cytotoxicity or antitumor effects of DOX in breast cancer lines or in a mouse model of breast cancer, but it did attenuate the decreases in left ventricular diastolic volume induced by acute DOX treatment.

conclusionsThis study identified the molecular and cellular signature of dose-dependent, DOX-mediated cardiotoxicity and provided evidence that PKR-1 is a promising target to combat cardiotoxicity of cancer treatments.

Indexed as

breast cancerDMSO, dimethyl sulfoxidedoxorubicinEC, endothelial cellEDPC, epicardium-derived progenitor cellEF, ejection fractionendothelial dysfunctionepicardial progenitor cellsFS, fractional shorteningGPCR, G-protein–coupled receptorHAEC, human aortic endothelial cellheart failureHF, heart failureHFrEF, heart failure with reduced ejection fractionMAPK, mitogen-activated protein kinaseNRF2, nuclear factor, erythroid 2 like 2 (also known as NFE2L2)PECAM, platelet and endothelial cell adhesion moleculePKR1-KO, prokineticin receptor 1 knockout micePKR1, prokineticin receptor-1 (also known as PROKR1)PROK1, prokineticin 1PROK2, prokineticin 2TUNEL, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling

Identifiers

PMID34396166
PMCPMC8352030
OpenAlexW2972205189

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.