心肌和外周淋巴细胞中β肾上腺素能受体和 G 蛋白偶联受体激酶在心移植中的转录组学分离。

Myocardial and peripheral lymphocytic transcriptomic dissociation of beta-adrenoceptors and G protein-coupled receptor kinases in heart transplantation.

机构信息

Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Plaza Mestre Vicente Ballester 2-13, Valencia, Spain.

出版信息

J Heart Lung Transplant. 2009 Nov;28(11):1166-71. doi: 10.1016/j.healun.2009.06.003. Epub 2009 Sep 26.

DOI:10.1016/j.healun.2009.06.003

PMID:19782607

Abstract

BACKGROUND

The genetic expression of adrenergic receptors plays an important pathophysiologic role in heart failure. G protein-coupled receptor kinases (GRKs) desensitize the beta-receptor to catecholaminergic stimulation. It has been suggested that their mRNA expression in peripheral lymphocytes could mirror the changes in their myocardial expression in the failing heart, but this relationship between the myocyte and lymphocyte has not been studied in heart transplantation (HT). The objective of this study was to analyze adrenergic receptor and GRK mRNA expression in myocardium and lymphocytes and their correlation.

METHODS

Twenty-three HT patients without evidence of acute rejection or echocardiographic dysfunction were assessed. Myocardial biopsy samples and peripheral blood lymphocytes were obtained, and alpha(1)- and beta-adrenoceptor subtype and GRK subtype mRNA was analyzed using reverse transcript-polymerase chain reaction (RT-PCR).

RESULTS

Mean age was 45 +/- 15 years, with a median of time since HT of 205 (351) days. In biopsies, the beta(1)/beta(2)-adrenoceptor ratio was 57%/42%, and GRK5 was the most commonly expressed, followed by GRK2. In lymphocytes, the beta(1)/beta(2) ratio was 3%/96%, whereas GRK2 mRNA expression was greater than that of other subtypes. There was no correlation between myocardial and lymphocyte parameters. There were no correlations with clinical variables, but lymphocyte beta(2) and GRK2 were increased with time since HT.

CONCLUSIONS

In the transplanted heart, there is no correlation between mRNA expression of adrenoceptors and GRKs in myocardium and peripheral lymphocytes. With time since transplant, mRNA expression of lymphocyte but not myocardial beta(2)-adrenoceptor and GRK2 increases. Therefore, this dissociation between myocardial and lymphocyte mRNA expression limits the potential use of peripheral blood samples for diagnosis of graft dysfunction.

摘要

背景

肾上腺素能受体的基因表达在心力衰竭的病理生理中起着重要作用。G 蛋白偶联受体激酶（GRK）使β受体对儿茶酚胺刺激脱敏。有人认为，外周淋巴细胞中的 mRNA 表达可以反映衰竭心脏中其心肌表达的变化，但这种心肌与淋巴细胞之间的关系在心脏移植（HT）中尚未研究过。本研究的目的是分析心肌和淋巴细胞中肾上腺素能受体和 GRK 的 mRNA 表达及其相关性。

方法

评估了 23 例无急性排斥反应或超声心动图功能障碍证据的 HT 患者。获取心肌活检样本和外周血淋巴细胞，并用逆转录聚合酶链反应（RT-PCR）分析α（1）-和β-肾上腺素能受体亚型和 GRK 亚型 mRNA。

结果

平均年龄为 45 ± 15 岁，HT 后中位数时间为 205（351）天。在活检中，β（1）/β（2）-肾上腺素能受体比值为 57%/42%，GRK5 是最常见的表达，其次是 GRK2。在淋巴细胞中，β（1）/β（2）比值为 3%/96%，而 GRK2 mRNA 表达高于其他亚型。心肌和淋巴细胞参数之间没有相关性。与临床变量也没有相关性，但淋巴细胞β（2）和 GRK2 随 HT 后时间的延长而增加。