title: MicroRNA profiling of atrial fibrillation in canines: miR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1.
abstract: BACKGROUND
  A critical mechanism in atrial fibrillation (AF) is cardiac autonomic nerve remodeling (ANR). MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Numerous miRNAs are involved in diseases of the nervous and cardiovascular systems.
  
  
  OBJECTIVE
  We aimed to assess the underlying role of miRNAs in regulating cardiac ANR in AF by right atrial tachypacing (A-TP) in canines.
  
  
  RESULTS
  Following 4-week A-TP, the superior left ganglionated plexuses (SLGPs), which are embedded in the fat pads of the left atrium, were subjected to miRNA expression profiling to screen preferentially expressed miRNAs. Sixteen miRNAs showed significantly differential expression between the control and A-TP groups, including miR-206, miR-203, miR-224 and miR-137. In particular, we focused on miR-206, which was elevated ~10-fold in A-TP dogs. Forced expression of miR-206 through lentiviral infection based on A-TP in vivo significantly shortened the atrial effective refractory period (AERP) (81 ± 7 vs. 98 ± 7 ms, P < 0.05). Immunohistochemical analysis showed that the regeneration of nerves increased more than 2-fold by miR-206 overexpression (P < 0.01). The expression of superoxide dismutase 1 (SOD1) was repressed by miR-206 overexpression by Western blot and luciferase assay, indicative of SOD1 as a direct target of miR-206. Overexpression of miR-206 increased reactive oxygen species (ROS) levels in vitro and in vivo, whereas miR-206 silencing attenuated irradiation- or A-TP-induced ROS. Knockdown of SOD1 effectively abolished ROS reduction caused by miR-206 silencing.
  
  
  CONCLUSIONS
  Our results found the differential expression of miRNAs in response to ANR in AF and elucidated the important role of miR-206 by targeting SOD1. The study illustrated the novel molecular mechanism of ANR and indicated a potential therapeutic target for AF.
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China; School of Medicine, Shandong University, No. 44, Wenhua Xi Road, Jinan, 250012, China.
authors: Yujiao
authors: Y
authors: Zhang
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China; School of Medicine, Shandong University, No. 44, Wenhua Xi Road, Jinan, 250012, China.
authors: Shaohua
authors: S
authors: Zheng
authors: School of Radiation Medicine and Protection, Soochow University, No. 199, Renai Road, Suzhou, 215123, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, No. 199, Renai Road, Suzhou, 215123, China.
authors: Yangyang
authors: Y
authors: Geng
authors: School of Radiation Medicine and Protection, Soochow University, No. 199, Renai Road, Suzhou, 215123, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, No. 199, Renai Road, Suzhou, 215123, China.
authors: Jiao
authors: J
authors: Xue
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China.
authors: Zhongsu
authors: Z
authors: Wang
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China.
authors: Xinxing
authors: X
authors: Xie
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China.
authors: Jiangrong
authors: J
authors: Wang
authors: School of Radiation Medicine and Protection, Soochow University, No. 199, Renai Road, Suzhou, 215123, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, No. 199, Renai Road, Suzhou, 215123, China.
authors: Shuyu
authors: S
authors: Zhang
authors: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, China.
authors: Yinglong
authors: Y
authors: Hou
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D017776:Autonomic Pathways / Q000503:physiopathology; D002478:Cells, Cultured; D004283:Dog Diseases / Q000235:genetics* / Q000503:physiopathology; D004285:Dogs; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D035683:MicroRNAs; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1