Myosin Light Chain Gene Expression Associated with Disease States of the Human Heart

Abstract During development of the human heart, the atrial isoform of alkali myosin light chain (MLC1 A ) is expressed in the ventricle. With maturation of the heart, MLC1 A expression is completely replaced by that of the adult ventricular myosin light chain, MLC1 V . We have evaluated the re-expression of MLC1 A as a marker of different disease states of the human ventricle. RNA was isolated from the ventricles of patients with idiopathic dilated cardiomyopathy (CM) and severe congenital cardiac defects (CCD). Northern blot analysis was used to measure the mRNA levels MLC1 A and MLC1 V in these samples. As a control, the level of regulatory MLC2 V mRNA was also measured. We find that the level of MLC2 V mRNA per μg total ventricular RNA is very similar in CM, CCD and normal human samples. In contrast, we find that MLC1 V mRNA levels tend to be reduced in both CM and CCD samples. In this case of the CCD samples, this apparent drop in MLC1 V is compensated by expression of the developmental MLC1 A isoform. However, in CM patients in end-stage failure, expression of MLC1 A is barely detectable. The expression of MLC1 A in CCD samples may reflect an adaptive mechanism in response to cardiac overload. The failure to detect substantial MLC1 A expression in the CM samples may reflect the failure of such an adaptive mechanism.