Analysis of beta-adrenergic receptor mRN levels in human ventricular biopsy specimens by quantitative polymerase chain reactions: Progressive reduction of beta1-adrenergic receptor mRN in heart failure

Objectives. This study investigated the relation between the severity of heart failure and the extent of the reduction of beta1-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 beta1-adrenergic receptors. Downregulation of beta1-adrenergic receptors has been suggested to be caused by reductions in mRN levels. Methods. Because biopsy specimens were small and receptor mRNAs not abundant, mRN 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 not, vert, similar1,000-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 mRN as an endogenous control. Results. Beta1-adrenergic receptor mRN 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 good correlation between hemodynamic indicators of heart failure and beta1-adrenergic receptor mRN levels. In contrast, beta2-adrenergic receptor mRN levels were apparently unaffected by heart failure. Conclusions. Reduced beta1-adrenergic receptor mRN levels occur early in heart failure and can be detected in septal biopsy specimens during right heart catheterization. The reduction in beta1-adrenergic receptor expression may contribute to further loss of cardiac function.