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01-11-2013 | Original Article

Cardiovascular differentiation of imatinib and bosutinib in the rat

Authors: Jonathan R. Heyen, Wenyue Hu, Joseph Jamieson, Stephane Thibault, Minerva Batugo, Cho-Ming Loi, Leigh Ann Burns-Naas, Aileen D. McHarg, Bart Jessen

Published in: International Journal of Hematology | Issue 5/2013

Abstract

Imatinib and bosutinib were administered to rats for up to 6 months at clinically relevant exposures to investigate the effects on the cardiovascular system. Imatinib treatment resulted in increased volume, wall thickness and mass suggesting a hypertrophic heart in male and female rats at one and fivefold clinical exposures, respectively. Bosutinib treatment resulted in milder cardiac hypertrophy in female rats only at fivefold clinical exposures. Analysis of excised hearts and cultured myocytes demonstrated increased expression of hypertrophic genes with imatinib or analogs, but not bosutinib or c-Abl RNAi treatment. The current dataset suggests that cardiovascular liability of imatinib and bosutinib are differentiated preclinically and c-Abl independent.

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Title: Cardiovascular differentiation of imatinib and bosutinib in the rat
Authors: Jonathan R. Heyen
Wenyue Hu
Joseph Jamieson
Stephane Thibault
Minerva Batugo
Cho-Ming Loi
Leigh Ann Burns-Naas
Aileen D. McHarg
Bart Jessen
Publication date: 01-11-2013
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 5/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-013-1453-2

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