The activity of erbB2 and erbB4 heterodimers is essential for the maintenance of myocardial structure and function. Ventricular specific erbB4 deletion (erbB4 CKO) leads to dilated cardiomyopathy, characterized by the eccentric hypertrophic growth of cardiomyocytes with a 50% reduction in contractility. The erbB2-dependent hypertrophic pathway was revealed to be active in erbB4 CKO hearts as monitored by differential gene expression in DNA microarrays. Therefore, we investigated the relative incidence of erbB2 in the hypertrophic growth of erbB4-deficient myocardium. Towards this aim, the erbB4 CKO mouse was crossed into erbB2 heterozygous mice resulting in a murine model (named, erbB4 CKO; erbB2+/-) with a 50% partial reduction of erbB2 protein. In this setting, we found that the hypertrophic growth reflected as a 1.5 fold increase in of erbB4 CKO was not detected in erbB4 CKO; erbB2+/- mice. In addition, the remarkable expression level of hypertrophy-related genes (ANP, BNP) determined in erbB4 CKO was kept to a 1.5x increase in erbB4 CKO; erbB2+/- myocardium. The overall heart morphology was, to some extent, preserved compared to erbB4 CKO, indicating that the hypertrophic process was attenuated in the partial reduction of erbB2. This study suggests that in the absence of erbB4, the erbB2 may be active in a pathologic growth through EGF receptor and G-protein coupled receptors.
