A molecular mechanism improving the contractile state in human myocardial hypertrophy

Various molecular mechanisms are operative in altering the sarcomeric function of the heart under increased hemodynamic workload. Expression of the atrial isoform (ALC-1) of the essential myosin light chain, a shift from alpha-myosin heavy chain (MHC) to beta-MHC, increased phosphorylation of the regulatory myosin light chains and increased troponin I (TnI) phosphorylation have been reported to modulate cardiac contractility in rodents. TO ASSESS A POSSIBLE CONTRIBUTION OF THESE SARCOMERIC PROTEINS TO CARDIAC PERFORMANCE IN HUMAN MYOCARDIAL HYPERTROPHY, TWO DIFFERENT FORMS OF CARDIAC HYPERTROPHY WERE INVESTIGATED: 19 patients with hypertropic obstructive cardiomyopathy (HOCM) and 13 patients with aortic stenosis (AS) with marked left ventricular hypertrophy and normal systolic function. There was no change in MHC gene expression, regulatory myosin light chain or TnI phosphorylation status in normal heart (NH), HOCM and AS patients. However, patients with hypertrophied myocardium expressed ALC-1 that was not detectable in NH. ALC-1 protein expression correlated positively with the left ventricular ejection fraction. In patients with hypertrophied myocardium, there was a mean ALC-1 protein expression of 12.7+/-3% (range 3.6% to 32%). In humans, ALC-1 expression is in vivo a powerful molecular mechanism of the sarcomere to maintain or improve myocardial contractility under increased hemodynamic demands.