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Expression data from isolated perfused rat hearts exposed to doxorubicin

ABSTRACT: We used microarrays to detail transcriptional changes in the rat heart in response to doxorubicin, a chemotherapeutic drug known to induce cardiac disfunction/heart failure Keywords: treatment vs control

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE12260 | GEO | 2008/12/31

SECONDARY ACCESSION(S): PRJNA113641

REPOSITORIES: GEO

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Transcription profiling of rat hearts isolated perfused and exposed to doxorubicin

Project description:We used microarrays to detail transcriptional changes in the rat heart in response to doxorubicin, a chemotherapeutic drug known to induce cardiac disfunction/heart failure Experiment Overall Design: Langendorff perfusion of isolated hearts with/without doxorubicin

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Project description:Doxorubicin (Dox) is an effective chemotherapeutic agent against a broad range of tumors. However, a threshold dose of doxorubicin causes an unacceptably high incidence of heart failure and limits its clinical utility. We have established two models of doxorubicin cardiotoxicity in mice: 1) in an acute model, mice are treated with 15mg/kg of doxorubicin once; 2) in a chronic model, they receive 3mg/kg weekly for the first 12 of a total of 18 weeks. Using echocardiography, we have monitored left ventricular function of the mouse hearts during treatment in chronic model and seen the expected development of dilated cardiomyopathy (DCM). Treated mice showed histological abnormalities similar to those seen in patients with doxorubicin cardiomyopathy. To investigate transcriptional regulation in these models, we used a microarray we generated with over 5000 independent cDNA clones from murine heart and skeletal muscle. We have identified genes that respond to doxorubicin exposure in both model systems, and confirmed these results using real-time PCR. In the acute model, a set of genes is regulated early and rapidly returns to baseline levels, consistent with the half-life of doxorubicin. In the chronic model, which mimics the clinical situation much more closely, we identified dysregulated genes that implicate specific mechanisms of cardiac toxicity and may serve as biomarkers of doxorubicin induced dilated cardiomyopathy. Keywords: time course

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