[Molecular basis for heart failure].

Cardiac functions are regulated by both contractile proteins and calcium regulatory proteins. In cardiac hypertrophy, an increase in protein synthesis can be partitioned into an increase in both capacity and efficiency of synthesis. beta-cardiac myosin heavy chain (beta-MHC) isoform is predominantly expressed while alpha-MHC is suppressed in pressure overload hypertrophy. The SR Ca(2+)-ATPase is also markedly decreased in pressure overloaded hearts, while in thyrotoxic hearts both are increased. The signal transduction system in cardiac hypertrophy can be examined by stretching cardiac myocytes grown up on deformable membranes. In our analysis, stretching myocytes stimulated protein kinase C, MAP-II kinase and S6 kinase, all of which may lead to the induction of fetal-type cardiac genes and accelerated protein synthesis. Analyses of the subcellular mechanisms of cardiac hypertrophy will provide important insights into understanding of the molecular basis of heart failure.