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Effects of doxorubicin on myocardial expression of apolipoprotein-B.

Journal article
Authors Björn Redfors
Yangzhen Shao
Truls Råmunddal
Malin Lindbom
Margareta Scharin Täng
Pia Stillemark-Billton
Jan Borén
Elmir Omerovic
Published in Scandinavian Cardiovascular Journal
Volume 46
Issue 2
ISSN 1651-2006
Publication year 2012
Published at Wallenberg Laboratory
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Links www.tandfonline.com/doi/full/10.310...
Keywords Doxorubicin, Heart failure, Apolipoprotein B100, Acute myocardial infarction
Subject categories Cardiac and Cardiovascular Systems

Abstract

Objective: Doxorubicin (DOX) is an effective antitumor agent against a variety of human malignancies but is associated with deleterious side effects, including myocardial damage and heart failure. Myocardial apoB-containing lipoprotein (apoB) is upregulated post myocardial infarction and has been shown to be cardioprotective in this setting by unloading excessive lipid. The aim of this study was to investigate whether apoB expression is increased also in DOX-induced heart failure and whether apoB overexpression protects the heart in DOX-induced myocardial injury. Design: Cardiac function and energy metabolism was studied in mice and rats 24 hours after intraperitoneally administered DOX. Results: We found that the content of apoB was decreased in rat myocardium 24 hours after DOX injection. In contrast, apoB content was increased in the infarcted myocardium of rats 24 hours post ischemia-reperfusion. Moreover, transgenic mice overexpressing apoB had better cardiac function and lower intracellular lipid accumulation compared to wild type mice 24h post DOX. Conclusions: Our findings indicate that depression of the myocardial apoB system may contribute to DOX-induced cardiac injury and that overexpression of apoB is protective, not only in ischemically damaged myocardium, but also in DOX-induced heart failure.

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