The MRNA Genomics Change And Significance Of Important Ion Channel Proteins In Patients With Atrial Fibrillation

Objective:To investigate the mRNA genomics change and significance of important ion channel proteins in patients with atrial fibrillation(AF),to reveal the mechanism of electrical remodeling in atrial fibrillation and lay the foundation for intervention in future.Methods:The 90 patients with atrial fibrillation was choose to perform the radiofrequency ablation(30 cases in each paroxysmal,persistent and permanent atrial fibrillation subgroup)in Beijing Shijitan hospital between January 2012 and January 2015,90 subjects of healthy physical examination as normal control group,the coronary sinus blood and peripheral venous blood was taken for each patient in the operation before atrial fibrillation radiofrequency ablation(AF-RFA).The genome-wide mRNA expression profile was analysis with mRNA microarray chip,and the mRNA expression difference result for the major ion channel gene was further validated using Real-time PCR test.Results:Compared with normal control group,the genome-wide mRNA expression in peripheral blood in atrial fibrillation patients,553 mRNA expression level was up-regulated,1018 mRNA expression was down-regulated(P < 0.05).12 ion channel protein mRNA expression increased ? 2.0-fold,10 mRNA expression decreased ? 2.0-fold,in which of K+ channel gene KCNE4 KCND2,KCNN4 declined obviously,KCNA5 dropped 11.54-fold(P < 0.00001);KCNS3 KCNS1,KCNG1,KCNG7 and Ca++ channel gene CACNA2D3 increased significantly,while the If channel HCN3 and GJA9 gap junction protein gene mRNA expression was dramatically lowered.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 kinds of ion channel protein mRNA expression differences was ? 2.0-fold,and the KCNA5 gene expression was down by 8.13-fold.Conclusion:The down-regulation of IKur channel KCNA5 gene expression in AF patients is most obvious,and more potassium ion channel expression differences is also significant,so that the potassium ion channel reconstruction may play a dominant or much more important role in AF electrical remodeling.Other ion channels involved in neuroendocrine regulation,excitation contraction coupling and gene expression etc.,the relationship of which with atrial fibrillation remains to be further research.