Key result
Gene deletion of the kinin B1 receptor in mice improved doxorubicin-induced cardiac dysfunction and normalized apoptosis and inflammation markers compared to controls.
Why the study?
Does gene deletion of the kinin B1 receptor improve cardiac dysfunction and reduce inflammation and apoptosis in mice with doxorubicin-induced cardiomyopathy?
Does gene deletion of the kinin B1 receptor improve cardiac dysfunction and reduce inflammation and apoptosis in mice with doxorubicin-induced cardiomyopathy?
Gene deletion of the kinin B1 receptor attenuates cardiac dysfunction, inflammation, and apoptosis in a mouse model of doxorubicin-induced cardiomyopathy, suggesting B1R antagonists may have therapeutic potential.
Hypothesis-generating for B1R antagonism in chemotherapy cardiotoxicity; requires human trials before any clinical consideration.
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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Westermann et al. (2008) studied Doxorubicin-induced cardiomyopathy. Gene deletion of the kinin B1 receptor (B1R(-/-)) vs. DOX control mice was evaluated on Cardiac dysfunction, inflammation, and apoptosis. Gene deletion of the kinin B1 receptor in mice improved doxorubicin-induced cardiac dysfunction and normalized apoptosis and inflammation markers compared to controls.
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