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August 11, 2021Life SciencesOpen Access

Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function

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Key result

Doxorubicin treatment in mice induced significant reactive oxygen species production in the left heart but not the right, with transcriptional changes correlating with myocardial dysfunction.

Why the study?

Heart failure limits doxorubicin use in cancer therapy, prompting investigation into differential left and right ventricular gene expression profiles in mice with preserved versus impaired myocardial function.

Does doxorubicin induce differential transcriptional changes and ROS production in the left and right ventricles of mice with preserved vs impaired cardiac function?

Population

48 male mice

Comparison

Doxorubicin responding vs non-responding animals

Design

Preclinical animal study

Follow-up

One week after the final dose

Authors

PSPaul StammIKIna KirmesAPAlexander Palmer

Discussion

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Member takes

Overview

May identify targets against doxorubicin cardiotoxicity; leaves open clinical translation pending prospective validation.

Structured PICO

Does doxorubicin induce differential transcriptional changes and ROS production in the left and right ventricles of mice with preserved vs impaired cardiac function?

P
Population
48 male mice treated with chronic low-dose doxorubicin over 4 weeks to evaluate differential gene expression and ROS production in the left and right ventricles.
I
Intervention
Chronic low dose doxorubicin administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks)
C
Comparator
Mice separated according to functional parameters into doxorubicin responding (impaired function) and non-responding (preserved function) animals
O
Outcome
Reactive oxygen species (ROS) production and gene expression profiling in separated right and left heartssurrogate

Doxorubicin induces differential gene expression and ROS production in the left versus right heart, correlating with the occurrence of myocardial dysfunction in a mouse model.

Cite This Study

Stamm et al. (2021) studied Doxorubicin-induced heart failure (n=48). Doxorubicin was evaluated on Reactive oxygen species (ROS) production and gene expression profiling. Doxorubicin treatment in mice induced significant reactive oxygen species production in the left heart but not the right, with transcriptional changes correlating with myocardial dysfunction.

synapsesocial.com/papers/6a74d8051078cf7de2b1dfc8https://doi.org/10.1016/j.lfs.2021.119879
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Transcriptional analysis of doxorubicin-induced cardiotoxicity2005 · 97 citations
  2. 2Topoisomerase IIβ–Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane2007 · 620 citations
  3. 3An Analysis of the Global Expression of MicroRNAs in an Experimental Model of Physiological Left Ventricular Hypertrophy2014 · 61 citations
  4. 4Prevention of Anthracycline-Induced Cardiotoxicity2014 · 685 citations
  5. 5Cancer Therapy–Related Cardiac Dysfunction and Heart Failure2016 · 337 citations