Impact of myosin heavy chain isoform expression and cardiac disease on cross-bridge cycling kinetics

The development and progression of cardiac disease was investigated by measurement of myofilament activation, tension development and cross-bridge cycling kinetics in two models of cardiac disease. Central to this investigation was accurate determination of myosin heavy chain (MHC) content of the myocardial tissue and the impact of expression of β-MHC on depression of cross-bridge cycling kinetics. Initial studies demonstrated a linear relationship between MHC isoform expression patterns and the depression of cross-bridge cycling in rat myocardium.;Extension of these findings to cardiac disease development allowed us to index the observed depression of myofilament function as a function of MHC isoform content. In a rodent model of congestive hear failure, we determined that there was a significant depression of cross-bridge cycling kinetics that could not be explained by the MHC isoform expression pattern. Thus, there are further underlying deleterious modifications that result in the depression of myofilament function and cardiac energetics that are present in end-stage congestive heart failure. However, in experimental diabetic cardiomyopathy, we determined the depression of cross-bridge cycling kinetics was linearly correlated with altered MHC isoform expression, such that the depressed cardiac energetics could be fully explained by altered MHC content. Thus, cross-bridge cycling kinetics are negatively impacted by altered MHC isoform expression, however, depression of cardiac energetics is not always directly correlated with such altered expression.