Engelhardt S, Böhm M, Erdmann E, Lohse M J
Laboratorium für Molekulare Biologie, Universität München, Germany.
J Am Coll Cardiol. 1996 Jan;27(1):146-54. doi: 10.1016/0735-1097(95)00425-4.
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.
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.
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.
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.
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.
本研究调查了心力衰竭严重程度与不同程度心力衰竭患者心导管检查期间获取的室间隔活检标本中β1 - 肾上腺素能受体信使核糖核酸（mRNA）水平降低程度之间的关系。
心力衰竭伴有β - 肾上腺素能受体系统脱敏，部分原因是β1 - 肾上腺素能受体下调。有人提出β1 - 肾上腺素能受体下调是由mRNA水平降低引起的。
由于活检标本较小且受体mRNA含量不丰富，通过定量逆转录/聚合酶链反应测定mRNA水平。该方法通过测量合成核糖核酸（RNA）标准品和通过溶液杂交测定法检测的移植心脏样本进行验证。两种方法结果相似，但聚合酶链反应法的灵敏度约高1000倍。对聚合酶链反应中的变异来源进行了定量分析，发现通过测定甘油醛 - 3 - 磷酸脱氢酶mRNA作为内对照可最佳控制这些变异。
活检标本中β1 - 肾上腺素能受体mRNA水平在轻度心力衰竭（纽约心脏协会心功能II级）时降低7%，中度心力衰竭（心功能III级）时降低26%，重度心力衰竭（心功能IV级）时降低>50%。心力衰竭的血流动力学指标与β1 - 肾上腺素能受体mRNA水平之间存在良好的相关性。相比之下，β2 - 肾上腺素能受体mRNA水平显然不受心力衰竭影响。
β1 - 肾上腺素能受体mRNA水平在心力衰竭早期即降低，且在右心导管检查期间可在间隔活检标本中检测到。β1 - 肾上腺素能受体表达的降低可能导致心功能进一步丧失。
