c-myc gene expression is localized to the myocyte following hemodynamic overload in vivo.

Expression of the proto-oncogene c-myc increases in the hemodynamically overloaded heart, but expression by cardiac myocytes has not been shown. To address this issue, right ventricular overload was induced in cats by pulmonary artery banding. Expression of c-myc and alpha-skeletal actin mRNA were determined by Northern analysis. Immuno-reactive Myc protein was identified by histochemical staining. Steady state levels of c-myc mRNA peaked within 2 h after banding. Levels of alpha-skeletal actin mRNA were maximally increased 48 h-1 week after banding and were still elevated at 1 month. Prominent staining of myocyte nuclei for immunoreactive Myc protein was detected 48 h after banding although a few interstitial nuclei were also positive. These studies show that c-myc and alpha-skeletal actin gene expression are upregulated in a large animal model of hemodynamic overload. The localization of the immunoreactive Myc protein to right ventricular myocyte nuclei after pulmonary artery banding supports the hypothesis that c-myc induction is part of a general response in cardiac hypertrophy that is common to many mammalian species.