| Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor. | |
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MedLine Citation:
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PMID: 18627295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Clinical use of the anthracycline doxorubicin (DOX) is limited by its cardiotoxic effects, which are attributed to the induction of apoptosis. To elucidate the possible role of the kinin B1 receptor (B1R) during the development of DOX cardiomyopathy, we studied B1R knockout mice (B1R(-/-)) 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 bax/bcl2 ratio in Western blots, indicating cardiac apoptosis. Furthermore, mRNA levels of the proinflammatory cytokine interleukin 6 were increased in the cardiac tissue. In DOX B1R(-/-) mice, cardiac dysfunction was improved compared to DOX control mice, which was associated with normalization of the bax/bcl-2 ratio and interleukin 6, as well as AKT activation state. These findings suggest that B1R is detrimental in DOX cardiomyopathy in that it mediates the inflammatory response and apoptosis. These insights might have useful implications for future studies utilizing B1R antagonists for treatment of human DOX cardiomyopathy. |
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Authors:
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Dirk Westermann; Olga Lettau; Meike Sobirey; Alexander Riad; Michael Bader; Heinz-Peter Schultheiss; Carsten Tschöpe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biological chemistry Volume: 389 ISSN: 1431-6730 ISO Abbreviation: Biol. Chem. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-09-04 Completed Date: 2008-09-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9700112 Medline TA: Biol Chem Country: Germany |
Other Details:
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Languages: eng Pagination: 713-8 Citation Subset: IM |
Affiliation:
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Charité-Universitätsmedizin Berlin, Department of Cardiology and Pneumology, Campus Benjamin Franklin, D-12200 Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Cardiomyopathies / complications, etiology, metabolism*, pathology* Doxorubicin / adverse effects* Gene Deletion* Hemodynamics Inflammation / etiology, metabolism*, pathology, physiopathology Mice Mice, Knockout Proto-Oncogene Proteins c-akt / metabolism Receptor, Bradykinin B1 / genetics*, metabolism* Receptor, Bradykinin B2 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Receptor, Bradykinin B1; 0/Receptor, Bradykinin B2; 23214-92-8/Doxorubicin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
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