MRNA genomics change and significance of important ion channel proteins in patients with atrial fibrillation

Abstract

Objective: 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. Methods: 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. Results: 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 (P< 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 (P<0.05), and other ion channel mRNA expressions were down-regulated (P<0.05). KCNA5 was down-regulated most obvious. Conclusion: 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.