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 veloc ity 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/dt(max)) 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 analys is. Results The value of + dT/dt(max) in CHF and LVH group were 64.17% and 37.1 5% lower than sham-operated controls (Sham) (P<0.01); values in the CHF gro up were 42.99% lower than that of LVH (P <0.01). The level of alpha -MHC mR NA 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 lev el 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 high er than that in LVH and Sham respectively (P<0.01). The ratio of <alpha>-MH C/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 mR NA level and + dT/dt(max) 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/dt(max) in CHF and LVH my ocardium. The decreased ratio of alpha -MHC/beta -MHC mRNA in LVH was mainl y due to the up regulation of beta -MHC mRNA while in CHF both down regulat ion of alpha -MHC and up regulation of beta -MHC were involved.