Expression of atrial myosin light chains but not alpha-myosin heavy chainsis correlated in vivo with increased ventricular function in patients withhypertrophic obstructive cardiomyopathy

The adult rodent heart adapts to increased work load by reexpression of its fetal genes, for example, beta-myosin heavy chain (MHC), in order to impro ve contractile function. However, the human ventricle regulates contractili ty by expression of atrial essential myosin light chain (ALC-1) rather than beta-MHC. We evaluated the impact of both mechanisms in patients with hype rtrophic cardiomyopathy. MHC isoform expression was quantified at the mRNA and protein levels by reverse transcriptase polymerase chain reaction and i mmunoblotting, respectively. Although alpha-MHC mRNA was detected in contro l and hypertrophied human ventricular tissue, alpha-MHC protein was not obs erved. Similarly, we investigated the expression of ALC-1 by two-dimensiona l polyacrylamide gel electrophoresis and the clinical and hemodynamic param eters of the patients with hypertrophic cardiomyopathy. We found a signific ant positive correlation between ALC-1 protein expression and dP/dt(max) in the hypertrophied human ventricle in vivo. Correlations between dP/dt(max) and expression of protein for the ryanodine receptor and L-type Ca2+ chann el were excluded. Our data suggest that reexpression of ALC-1 improves the contractile state of the adult human heart. We propose that two evolutionar ily divergent compensatory mechanisms for increased work demand exist in th e mammalian heart: MHC regulation in rodents and essential MLC regulation, of cardiac contractility, in humans.