Myosin heavy chain gene expression in human heart failure.
Two isoforms of myosin heavy chain (MyHC), alpha and beta, exist in the mammalian ventricular myocardium, and their relative expression is correlated with the contractile velocity of cardiac muscle. Several pathologic stimuli can cause a shift in the MyHC composition of the rodent ventricle from alpha- to beta-MyHC. Given the potential physiological consequences of cardiac MyHC isoform shifts, we determined MyHC gene expression in human heart failure where cardiac contractility is impaired 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 disease or structural cardiovascular abnormalities. This group consisted of seven patients with nonfailing (NF) hearts and seven patients with hearts that exhibited donor heart dysfunction (DHD). These were compared with 19 patients undergoing cardiac transplantation for chronic end-stage heart failure (F). The relative amounts of alpha-MyHC mRNA to total (i.e., alpha + beta) MyHC mRNA in the NF- and DHD-LVs were surprisingly 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). There 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 chronic end-stage heart failure. If protein and enzymatic activity correlate with mRNA expression, this molecular alteration may be sufficient to explain systolic dysfunction in F-LVs, and therapeutics oriented towards increasing alpha-MyHC gene expression may be feasible.
Nakao
K
K
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.
Minobe
W
W
Roden
R
R
Bristow
M R
MR
Leinwand
L A
LA
D000328:Adult; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000235:genetics*; D009218:Myosins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014019:Tissue Donors
D012333:RNA, Messenger; D018995:Myosin Heavy Chains; D009218:Myosins