人类心房颤动中L型钙通道和肌浆网Ca(2+)-ATP酶mRNA下调，而雷诺丁受体、肌集钙蛋白和受磷蛋白的mRNA无显著变化：对心房电重构机制的深入了解

Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling.

作者信息

Lai L P, Su M J, Lin J L, Lin F Y, Tsai C H, Chen Y S, Huang S K, Tseng Y Z, Lien W P

机构信息

Pharmacological Institute, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei.

出版信息

J Am Coll Cardiol. 1999 Apr;33(5):1231-7. doi: 10.1016/s0735-1097(99)00008-x.

DOI:10.1016/s0735-1097(99)00008-x

PMID:10193721

Abstract

OBJECTIVES

We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation.

BACKGROUND

Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear.

METHODS

A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase.

RESULTS

The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation.

CONCLUSIONS

L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

摘要

目的

我们研究了包括L型钙通道、肌浆网钙腺苷三磷酸酶（Ca(2+)-ATP酶）、兰尼碱受体、肌集钙蛋白和受磷蛋白在内的钙处理基因在人类心房颤动中的基因表达情况。

背景

最近的研究表明，心房颤动时的心房电重构与细胞内钙超载有关。然而，钙处理蛋白的变化仍不清楚。

方法

共纳入34例接受心脏直视手术的患者。分别从右心房游离壁、右心耳、左心房游离壁和左心耳获取心房组织。通过逆转录-聚合酶链反应测量基因的信使核糖核酸（mRNA）量，并将其标准化为甘油醛3-磷酸脱氢酶的mRNA水平。

结果

持续性心房颤动超过3个月的患者中，L型钙通道和Ca(2+)-ATP酶的mRNA显著降低（L型钙通道：0.36±0.26对0.90±0.88；Ca(2+)-ATP酶：0.69±0.42对1.21±0.68；两者p<0.05，所有数据为任意单位）。我们进一步证明，四个心房组织采样部位之间基因表达无空间差异。年龄、性别和基础心脏病对基因表达无显著影响。相比之下，心房颤动时兰尼碱受体、肌集钙蛋白和受磷蛋白的mRNA水平无显著变化。