Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.
Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysfunction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment of myocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters.min-1.m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment alpha-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.
Ladenson
P W
PW
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Sherman
S I
SI
Baughman
K L
KL
Ray
P E
PE
Feldman
A M
AM
D000199:Actins / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D013960:Thyroid Function Tests; D000099211:Phospholamban
D000199:Actins; D000251:Adenosine Triphosphatases; D009320:Atrial Natriuretic Factor; D002135:Calcium-Binding Proteins; D004247:DNA; D009218:Myosins; D009838:Oligodeoxyribonucleotides; D012313:RNA; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000099211:Phospholamban