Alterations in myosin heavy chain isoform gene expression during the transition from compensatory hypertrophy to congestive heart failure in rats

OBJECTIVE: To explore the molecular mechanism underlying the decreased velocity of tension rise in rat myocardium during congestive heart failure (CHF) and left ventricular hypertrophy (LVH) induced by aortic stenosis. METHODS: The maximum velocity of tension rise (+dT/dtmax) was measured in left ventricular papillary muscle and the mRNA level of myosin heavy chain (MHC) isoforms in the left ventricle were detected by Northern blot analysis. RESULTS: The value of +dT/dtmax in CHF and LVH group were 64.17% and 37.15% lower than sham-operated controls (Sham) (P < 0.01); values in the CHF group were 42.99% lower than that of LVH (P < 0.01). The level of alpha-MHC mRNA in LVH was not different from that of the Sham (P > 0.05), but decreased significantly in CHF to 42.3% of Sham and 56.1% of LVH (P < 0.01). The level of beta-MHC mRNA was up-regulated by 88.3% (P < 0.01) in LVH compared with Sham and the level of beta-MHC in CHF was 1.5-fold and 3.7-fold higher than that in LVH and Sham respectively (P < 0.01). The ratio of alpha-MHC/beta-MHC mRNA in LVH and CHF decreased to 42.4% and 9.8% respectively of the value in Sham (P < 0.01). Correlation between alpha-MHC/beta-MHC mRNA level and +dT/dtmax was analyzed which showed that these values were positively correlated with a correlation coefficient of 0.875 (P < 0.01). CONCLUSION: The decreased ratio of alpha-MHC/beta-MHC mRNA was the major molecular mechanism underlying the decreased +dT/dtmax in CHF and LVH myocardium. The decreased ratio of alpha-MHC/beta-MHC mRNA in LVH was mainly due to the up regulation of beta-MHC mRNA while in CHF both down regulation of alpha-MHC and up regulation of beta-MHC were involved.