GENE EXPRESSION PROFILING ON THE ERBB4 MURINE MODEL OF DILATED CARDIOMYOPATHY

HERTIG CM, BUITRAGO-EMANUEL E, MALVICINI M, WITT H, RUIZ P.

Misiones

Congreso; LV Reunion Anual de la Sociedad Argentina de Investigación Bioquimica; 2004

Sociedad Argentina de Investigación Bioquímica

Dilated cardiomyopathy (DCM) is a leading cause of heart failure that is believed to result from abnormal remodeling of cardiac tissue in response to a variety of stressors. Receptor proteintyrosine kinase erbB4 activities are essential for the maintenance of normal heart function as the significant loss of erbB4 in ventricular muscle leads to a severe DCM. We performed gene expression analyses in ventricular samples from the conditional erbB4 knockout mouse (erbB4 CKO) utilizing DNA micro-arrays. Differentially expressed genes, comprising more than 1.000, were functionally grouped and compared to gene expression from other forms of mouse DCM. Taken together these results showed significant changes in the expression pattern of genes involved in the hypertrophic response (re-expression of the fetal cell program), and required for the maintenance of the cardiomyocyte architecture and junction. Modifications in these structures are representative of a pathological remodeling of the myocardium. We have extended this analysis to examine the expression pattern of candidate genes in models of acquired DCM. For example, the severe cardiomyopathy displayed in a subset of breast cancer patients undergoing combined treatments with antibodies blocking the neuregulin signaling pathway and anthracycline derivatives.