Abstract
OBJECTIVES. This study investigated the relation between the severity
of heart failure and the extent of the reduction of beta 1-adrenergic
receptor messenger ribonucleic acid (mRNA) levels in biopsy specimens
from the ventricular septum obtained during cardiac catheterization
of patients with various degrees of heart failure. BACKGROUND. Heart
failure is accompanied by desensitization of the beta-adrenergic
receptor system, which is in part due to downregulation of beta 1-adrenergic
receptors. Downregulation of beta 1-adrenergic receptors has been
suggested to be caused by reductions in mRNA levels. METHODS. Because
biopsy specimens were small and receptor mRNAs not abundant, mRNA
levels were determined by quantitative reverse transcription/polymerase
chain reactions. This method was validated by measuring synthetic
ribonucleic acid (RNA) standards and samples from explanted hearts
by solution hybridization assays. Both methods yielded similar results,
but the polymerase chain reaction method was approximately 1,000-fold
more sensitive. Sources of variations in the polymerase chain reaction
were quantitated and found to be best controlled for by determination
of the glyceraldehyde phosphate dehydrogenase mRNA as an endogenous
control. RESULTS. Beta 1-adrenergic receptor mRNA levels in the biopsy
specimens were decreased by 7% in mild (New York Heart Association
functional class II), 26% in moderate (functional class III) and
> 50% in severe heart failure (functional class IV). There was a
good correlation between hemodynamic indicators of heart failure
and beta 1-adrenergic receptor mRNA levels. In contrast, beta 2-adrenergic
receptor mRNA levels were apparently unaffected by heart failure.
CONCLUSIONS. Reduced beta 1-adrenergic receptor mRNA levels occur
early in heart failure and can be detected in septal biopsy specimens
during right heart catheterization. The reduction in beta 1-adrenergic
receptor expression may contribute to further loss of cardiac function.
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