Endothelin Stimulates Cardiac Alpha- and Beta- Myosin Heavy Chain Gene Expression

The effect of endothelin-1 on cardiac myosin heavy chain gene expression was examined using an isolated neonatal rat myocardial cell culture system. The effects of endothelin-1 on the expression of alpha- and beta- myosin heavy chain genes in the primary rat myocardial cell culture system were examined by S1 nuclease protection analysis. Endothelin-1 was found to stimulate both alpha- and beta- myosin heavy chain gene expression. The 5' flanking regions of both the alpha- and beta- myosin heavy chain gene promoters ligated to a reporter gene, chloramphenicol acetyltransferase, were used to study the effect of endothelin-1 on transcription. Myocardial cells treated with endothelin-1 increased the transcription rate of alpha- and beta- myosin heavy chain genes in a dose-dependent manner. Thus, the hypertrophic effect of endothelin-1 on cardiac myocytes involves augmentation of alpha- and beta- myosin heavy chain gene expression by increasing gene transcription.