Alterations in the expression of myosin heavy chain isoforms in hypoxia-induced hypertrophied ventricles in rats

Abstract

This study was designed to characterize cardiac changes in myosin heavy chain (MHC)-β, capacity for oxidative metabolism and muscle mass in hearts of rats born and raised at simulated altitudes (2200 m or 4000 m) compared to age-matched sea level controls. On the basis of electrophoretic analyses, we found that the hypoxia-induced ventricular hypertrophy produces a significant increase in MHC-β in both ventricles. Furthermore, we observed an exponential relationship between the mass of right ventricular muscle and percentages in the expression of MHC-β ( r=0.928, P<0.001). We also observed the reduction in the citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activities in both hypertrophied ventricles ( P<0.001). As a consequence, there were negative correlations between the percentage expression of MHC-β and the CS or HAD activities ( P<0.001). In contrast, there were no significant correlations between the relative expressions of MHC-β and either CS or HAD enzymatic activities in both ventricles after adjusting for the relative wet mass. In conclusion, the observed increases in MHC-β may be a compensation to augment efficiency if muscles contract in hypertrophied hearts where mitochondria fail to respond to increases in tissue mass. These findings suggest that the increased relative expression of MHC-β is a compensation to sustain cardiac contractile efficiency in response to impaired oxidative metabolism in the hypoxia-induced hypertrophied ventricles of rats.