Study Of Long Noncoding RNA Expression Profile In Patients With Rheumatic Heart Valve Disease Complicated With Sinus Rhythm And Atrial Fibrillation Rhythm

objective:Through investigating the expression difference of long non-coding RNA in auricular dextra of patients with rheumatic heart valve disease complicated with sinus rhythm and permanent atrial fibrillation,to provide fundamental data for further research the mechanism of atrial fibrillation and find new methods for prevention and treatment of atrial fibrillation.Methods:Five patients aged from 45 to 55 years with Rheumatic heart valve disease complicated with permanent atrial fibrillation were collected as experimental group and other five rheumatic heart valve disease patients aged from 46 to 54 years with sinus rhythm were collected as control group.All the patients in experimental group and control group had not taken any anti-arrhythmia and anti-heart failure medicines and the AF persisted at least one year in experimental group.The auricular dextra were harvested in the ten patients during the valve replacement surgery.After synthesizing cDNA with the qualified RNA and completing the Gene chip hybridization,scanning the hybridization chip to get the preliminary results.The analyzing data was converted by Statistical software to obtain the data of mRNA and lncRNA.With Fold Change>2,p<0.05 as incorporation criteria,differential expression spectrum of mRNA and LncRNA were obtained.To confirm the result of Chip scanning,QRT-PCR was used to validate the most deferentially expressed LncRNA.After clustering the data,Gene ontology categories(GO)analysis and kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were used to analyze the preliminary bio-informational function of these results.Results:A total of 333 lncRNAs were found to be deferentially expressed between experimental and control groups.Among them 119 were up-regulated(9 lncRNAs of these with Fold change>4,and NONHSAT040387 is the highest up-regulated one with Fold change up to 7.35)and 214 were down-regulated(14 LncRNAs with Fold change>4,TCONs00003502 is the most differently expressed one with Fold change equal to 8.18).Meanwhile,104 mRNAs were up-regulated(12 mRNAs' Fold change>4,CCL8 is highest expressed one with Fold change 20.8)and 74 mRNAs were down-regulated(7 mRNAs' Fold change>4,the highest Fold change is 8.9 which belongs to mRNA GLP1R).Analyzing the differently expressed mRNAs with Gene Ontology(GO)software,we found 289 differently expressed genes concentrate in biological process module.The most enriched Gene annotation is immune response.Similarly,122 differently expressed genes concentrate in cellular component with Plasma membrane as its most enriched annotation and 108 differently expressed genes concentrate in molecular function with transporter activity as its most enriched gene annotation.Pathway analysis showed 18 signal channels are regulated by differently expressed mRNAs and the most enriched signal channel is Cytokine-cytokine receptor interaction.Conclusions:lncRNA microarray analysis is an effective way to screen the differential expression difference of lncRNA and mRNA in rheumatic heart valve disease patients with sinus rhythm and AF.The result of QRT-PCR is consistent with chip scanning.Preliminary bio-informational analysis revealed that lncRNA was involved in the pathophysiology progress of AF.These results may provide a new way for further research of the mechanism and prevention and treatment of atrial fibrillation.