Figure 5.

Myocardial up-regulation of Bcl-2 prevents imatinib cardiotoxicity. (A) Cardiomyocyte-specific Bcl-2 overexpression in transgenic mice using the α-myosin heavy chain (MHC) promoter. (B) Expression of Bcl-2 was confirmed using northern (left panel) and western blots (right panel). Vs, ventricles; Ks, kidneys; Li, liver; Br, brain; Sk, skeletal muscle. (C) Left ventricular posterior wall thickness (LVPW) obtained by echocardiographic analysis in treated wild-type (Wt) and Bcl-2 transgenics (Tg) relative to their respective vehicle-treated controls. Data are the mean ± SEM of n = 4–6. (D) Histological sections from mice from the four different groups stained with ANF antibody and counterstained with methyl green. Note the cytoplasmic presence of the ANF stress marker (brown) in the ventricles of Wt imatinib-treated but not Bcl-2 mice. (E) Percentage of apoptotic nuclei as detected by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP end labelling) assays in Wt and Bcl-2 (Tg) mice treated with vehicle (V), imatinib (I), or doxorubicin (Dox). The data shown are the mean from four different mice per group.