Roles Of MicroRAN-101 In Atrial Remodeling Of Atial Fibrillation

Objective:To investigate the changes of microRNA-101 expression in human chronic atrial fibrillation(AF)and explore the roles of microRNA-101 in atrial remodeling of AF.Methods:Right atrial appendages were obtained from 54 patients,7 with congenital heart disease(CHD)and 47 with rheumatic heart disease(RHD).All of the patients divided into two groups,25 in sinus rhythm(SR)group and 29 patients in chronic AF group.The changes of morphological features and ultrastructure with right atrial tissues were observed by Hematein-Eosin(HE)staining and electron microscope respectively.Quantitative real time polymerase chain reaction(qRT-PCR)was applied to detect the expression ratio of microRNA-101 and its target gene Cx43 mRNA.Western blot was performed to measure the Cx43 protein.MiRNA-in situ hybridization was used to assess the localization and expression of microRNA-101.Masson staining was used to observe the accumulation of collagenous fiber.Results:Results of HE staining showed that increase in the size of atrial myocytes in AF patients,as well as damage of muscle and abnormal arrangement of cells,enlargement nuclei,interstitial fibrosis.Meanwhile,remodeling of microstructure was to be seen in AF group,such as activated and enlarged nuclei with dispersed chromatin,indistinct sarcoplasmic reticulum,swollen cristae and accumulation of glycogen.Compared patients with SR group,the expression level of microRNA-101 was significantly decreased in patients with AF group(relative expression:0.6157±0.1749 vs 2.2900±0.3992,P<0.01).Studies of Cx43 mRNA expression indicated that there was no statistical significance between SR and AF patients(relative expression:0.8253±0.2470 vs 1.1002±0.2603,P>0.05),while Cx43 protein was reduced in AF group(0.5710±0.2062)compared with SR group(1.1439±0.3750)(P<0.05).The result of miRNA-in situ hybridization showed that microRNA-101 in AF group was down-regulation by about 25.6%than that of SR group,and microRNA-101was specially expressed in collagenous fibers of mesenchyme,endocardium,epicardium and Virchow-Robin,less expression in myocardium.Results of masson staining showed increasing accumulation of collagenous fibers in AF group.Conclusion:Expression of microRNA-101 was down-regulated in AF patients and its target Cx43 protien was also decreased.This non-negative relationship between microRNA-101 and Cx43 may showed that microRNA-101 play an critical role in atial remodeling of AF not via regulate Cx43.MicroRNA-101 specially expressed in connective tissues may suggest that microRNA-101 involved in the physiopathological procedure of chronic AF via interrupting the metabolism of collagen and regulating the formation of fibrosis.