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[心房颤动患者重要离子通道蛋白的mRNA基因组学变化及意义]

[mRNA genomics change and significance of important ion channel proteins in patients with atrial fibrillation].

作者信息

Wang R P, Wang S, Chen D, Yang N, Lei L C, Wang Z Y, Ye H M, Ren L H, Yang S X

出版信息

Zhonghua Yi Xue Za Zhi. 2018 Oct 23;98(39):3171-3177. doi: 10.3760/cma.j.issn.0376-2491.2018.39.009.

Abstract

To investigate the mRNA genomics changes and significance of important ion channel proteins in patients with atrial fibrillation (AF), to reveal the mechanism of electrical remodeling in AF. Ninety patients with AF were chosen to receive the radiofrequency ablation (AF-RFA), 90 healthy subjects were included as the normal control group.The coronary sinus blood and peripheral venous blood were taken from each AF patient during the operation of AF-RFA.The genome-wide mRNA expression profile was analyzed with mRNA microarray chip, and the mRNA expression difference results for the major ion channel gene was further validated using Real-time PCR test. The expression of twelve ion channel protein mRNA increased ≥2.0-fold, expression of 10 mRNA decreased ≥2.0-fold, among which K(+) channel gene KCNE4, KCND2, KCNN4 declined obviously, KCNA5 dropped 11.54-fold (< 0.01); KCNS3, KCNS1, KCNG1, KCNG7 and Ca(+ +) channel gene CACNA2D3 increased significantly.Compared with autologous peripheral blood, 12 mRNAs of ion channel protein in coronary sinus blood of AF patients was differentially expressed ≥2.0-fold.Compared with control group in peripheral blood, 7 ion channel protein mRNA expression differences was ≥2.0-fold, and the KCNA5 gene expression was down by 8.13-fold.RT-PCR confirmed that the trend and extent of differential expression were consistent with the chip results.The results of myocardial tissue RT-PCR showed that CACNA1C, KCNC3, KCNG1 and KCNK7 mRNA were up-regulated in AF (<0.05), and other ion channel mRNA expressions were down-regulated (<0.05). KCNA5 was down-regulated most obvious. The down-regulation of KCNA5 gene expression in AF patients is most obvious, and more potassium ion channel expression differences are also significant, so that the potassium ion channel reconstruction may play a dominant or much more important role in AF electrical remodeling.

摘要

为探讨心房颤动(AF)患者重要离子通道蛋白的mRNA基因组学变化及其意义,揭示AF电重构机制。选取90例AF患者接受射频消融治疗(AF-RFA),90例健康受试者作为正常对照组。在AF-RFA手术过程中采集各AF患者的冠状窦血和外周静脉血。采用mRNA微阵列芯片分析全基因组mRNA表达谱,并通过实时荧光定量PCR检测进一步验证主要离子通道基因的mRNA表达差异结果。12种离子通道蛋白mRNA表达上调≥2.0倍,10种mRNA表达下调≥2.0倍,其中钾离子通道基因KCNE4、KCND2、KCNN4明显下降,KCNA5下降11.54倍(<0.01);KCNS3、KCNS1、KCNG1、KCNG7及钙离子通道基因CACNA2D3显著升高。与自体外周血相比,AF患者冠状窦血中12种离子通道蛋白mRNA差异表达≥2.0倍。与外周血对照组相比,7种离子通道蛋白mRNA表达差异≥2.0倍,KCNA5基因表达下降8.13倍。RT-PCR证实差异表达趋势和程度与芯片结果一致。心肌组织RT-PCR结果显示,AF患者心肌组织中CACNA1C、KCNC3、KCNG1和KCNK7 mRNA上调(<0.05),其他离子通道mRNA表达下调(<0.05)。KCNA5下调最为明显。AF患者中KCNA5基因表达下调最为明显,且更多钾离子通道表达差异也很显著,因此钾离子通道重构可能在AF电重构中起主导或更重要的作用。

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