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Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor

Item Type:Article
Title:Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
Creators Name:Westermann, D. and Lettau, O. and Sobirey, M. and Riad, A. and Bader, M. and Schultheiss, H.P. and Tschoepe, C.
Abstract:The clinical use of the anthracycline doxorubicin (Dox) is limited by its cardio toxic effects, which is attributed to the induction of apoptosis. To investigate the possible role of the B1 receptor during the development of Dox cardiomyopathy we studied B1 receptor knockout mice (B1(-/-)) by investigating cardiac inflammation and apoptosis after induction of DOX induced cardiomyopathy. DOX control mice showed cardiac dysfunction measured by pressure-volume loops in vivo. This was associated with a reduced activation state of AKT as well as an increased ratio of bax/bcl2 in western blots, as an indicator of cardiac apoptosis. Furthermore, the mRNA content of the pro inflammatory cytokine interleukin 6 was increased in the cardiac tissue. In Dox B1(-/-) cardiac dysfunction was improved compared to DOX control mice, which was associated with a normalization of the bax/bcl-2 ratio and interleukin 6 as well as AKT activation state. These findings suggest that the B1 receptor is detrimental in DOX cardiomyopathy in that it mediates inflammatory and apoptosis. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human DOX cardiomyopathy.
Keywords:Bradykinin, Cardiac Apoptosis, Cardiac Inflammation, Doxorubicin Cardiomyopathy, Animals, Mice
Source:Biological Chemistry
ISSN:1431-6730
Publisher:de Gruyter (Germany)
Volume:389
Number:6
Page Range:713-718
Date:June 2008
Official Publication:https://doi.org/10.1515/BC.2008.070
PubMed:View item in PubMed

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