Imatinib-induced changes in the expression profile of microRNA in the plasma and heart of mice-A comparison with doxorubicin
Language English Country France Media print-electronic
Document type Journal Article
PubMed
31004989
DOI
10.1016/j.biopha.2019.108883
PII: S0753-3322(19)30286-0
Knihovny.cz E-resources
- Keywords
- Biomarker, Cardiotoxicity, Doxorubicin, Imatinib, MicroRNA,
- MeSH
- Doxorubicin toxicity MeSH
- Imatinib Mesylate pharmacology MeSH
- MicroRNAs blood genetics metabolism MeSH
- Mice MeSH
- Gene Expression Regulation drug effects MeSH
- Heart drug effects MeSH
- Transcriptome drug effects MeSH
- Troponin T blood genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Doxorubicin MeSH
- Imatinib Mesylate MeSH
- MicroRNAs MeSH
- Troponin T MeSH
Cardiotoxicity is a serious adverse reaction to cancer chemotherapy and may lead to critical heart damage. Imatinib mesylate (IMB), a selective tyrosine kinase inhibitor, is sometimes accompanied by severe cardiovascular complications. To minimize risk, early biomarkers of such complications are of utmost importance. At the present time, microRNAs (miRNAs) are intensively studied as potential biomarkers of many pathological processes. Many miRNAs appear to be specific in some tissues, including the heart. In the present study we have explored the potential of specific miRNAs to be early markers of IMB-induced cardiotoxicity. Doxorubicin (DOX), an anthracycline with well-known cardiotoxicity, was used for comparison. NMRI mice were treated with IMB or DOX for nine days in doses corresponding to the highest recommended doses in oncological patients, following which plasmatic levels of miRNAs were analyzed in miRNA microarrays and selected cardio-specific miRNAs were quantified using qPCR. The plasmatic level of miR-1a, miR-133a, miR-133b, miR-339, miR-7058, miR-6236 and miR-6240 were the most different between the IMB-treated and control mice. Interestingly, most of the miRNAs affected by DOX were also affected by IMB showing the same trends. Concerning selected microRNAs in the hearts of individual mice, only miR-34a was significantly increased after DOX treatment, and only miR-205 was significantly decreased after IMB and DOX treatment. However, no changes in any miRNA expression correlated with the level of troponin T, a classical marker of heart injury.
Faculty of Medicine in Hradec Králové Charles University Šimkova 870 Hradec Králové Czech Republic
Faculty of Pharmacy Charles University Heyrovského 1203 Hradec Králové Czech Republic
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