Imatinib-induced changes in the expression profile of microRNA in the plasma and heart of mice-A comparison with doxorubicin.

Abstract

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.

• Authors: Barbora Hanousková, Mikuláš Skála, Veronika Brynychová, Tomáš Zárybnický, Veronika Skarková, Petra Kazimírová, Andrea Vernerová, Pavel Souček, Lenka Skálová, Radek Pudil, Petra Matoušková
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 115 Pg. 108883 (Jul 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 31004989 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• MicroRNAs
• Troponin T
• Doxorubicin
• Imatinib Mesylate

Topics

• Animals
• Doxorubicin (toxicity)
• Female
• Gene Expression Regulation (drug effects)
• Heart (drug effects)
• Imatinib Mesylate (pharmacology)
• Mice
• MicroRNAs (blood, genetics, metabolism)
• Transcriptome (drug effects)
• Troponin T (blood, genetics, metabolism)