Myosin light chain gene expression associated with disease states of the human heart.
During development of the human heart, the atrial isoform of alkali myosin light chain (MLC1A) is expressed in the ventricle. With maturation of the heart, MLC1A expression is completely replaced by that of the adult ventricular myosin light chain, MLC1V. We have evaluated the re-expression of MLC1A 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 of MLC1A and MLC1V in these samples. As a control, the level of regulatory MLC2V mRNA was also measured. We find that the level of MLC2V mRNA per microgram total ventricular RNA is very similar in CM, CCD and normal human samples. In contrast, we find that MLC1V mRNA levels tend to be reduced in both CM and CCD samples. In the case of the CCD samples, this apparent drop in MLC1V is compensated by expression of the developmental MLC1A isoform. However, in CM patients in end-stage failure, expression of MLC1A is barely detectable. The expression of MLC1A in CCD samples may reflect an adaptive mechanism in response to cardiac overload. The failure to detect substantial MLC1A expression in the CM samples may reflect the failure of such an adaptive mechanism.
Trahair
T
T
Department of Anatomy, University of Sydney, NSW, Australia.
Yeoh
T
T
Cartmill
T
T
Keogh
A
A
Spratt
P
P
Chang
V
V
dos Remedios
C G
CG
Gunning
P
P
D000328:Adult; D002303:Cardiac Output, Low / Q000378:metabolism; D015342:DNA Probes; D015870:Gene Expression; D006330:Heart Defects, Congenital / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D009218:Myosins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
D015342:DNA Probes; D012333:RNA, Messenger; D009218:Myosins