MYOSIN HEAVY-CHAIN GENE-EXPRESSION IN HUMAN HEART-FAILURE

Two isoforms of myosin heavy chain (MyHC), alpha and beta, exist in th e mammalian ventricular myocardium, and their relative expression is c orrelated with the contractile velocity of cardiac muscle. Several pat hologic stimuli can cause a shift in the MyHC composition of the roden t ventricle from alpha- to beta-MyHC. Given the potential physiologica l consequences of cardiac MyHC isoform shifts, we determined MyHC gene expression in human heart failure where cardiac contractility is impa ired significantly. In this study, we quantitated the relative amounts of alpha- and beta-MyHC mRNA in the left ventricular free walls (LVs) of 14 heart donor candidates with no history of cardiovascular diseas e or structural cardiovascular abnormalities. This group consisted of seven patients with nonfailing (NF) hearts and seven patients with hea rts that exhibited donor heart dysfunction (DHD). These were compared with 19 patients undergoing cardiac transplantation for chronic end-st age heart failure (F). The relative amounts of alpha-MyHC mRNA to tota l (i.e., alpha + beta) MyHC mRNA in the NF- and DHD-LVs were surprisin gly high compared with previous reports (33.3+/-18.9 and 35.4+/-16.5%, respectively), and were significantly higher than those in the F-LVs, regardless of the cause of heart failure (2.2+/-3.5%, P < 0.0001). Th ere was no significant difference in the ratios in NF-and DHD-LVs. Our results demonstrate that a considerable amount of alpha-MyHC mRNA is expressed in the normal heart, and is decreased significantly in chron ic end-stage heart failure. If protein and enzymatic activity correlat e with mRNA expression, this molecular alteration may be sufficient to explain systolic dysfunction in F-LVs, and therapeutics oriented towa rds increasing alpha-MyHC gene expression may be feasible.