title: MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model.
abstract: BACKGROUND
  The potential mechanisms of microRNA-1 (miR-1) in the electrical remodeling of atrial fibrillation remain unclear. The purpose of this study was to evaluate the effects of miR-1 on the atrial effective refractory period (AERP) in a right atrial tachypacing model and to elucidate the potential mechanisms.
  
  
  RESULTS
  QRT-PCR and western blot were used to detect the expression of the miR-1, KCNE1, and KCNB2 genes after 1-week of right atrial tachypacing in New Zealand white rabbits. The AERP was measured using a programmable multichannel stimulator, and atrial fibrillation was induced by burst stimulation in vivo. The slowly activating delayed rectifier potassium current (IKs) and AERP in atrial cells were measured by whole cell patch clamp in vitro. Right atrial tachypacing upregulated miR-1 expression and downregulated KCNE1 and KCNB2 in this study, while the AERP was decreased and the atrial IKs increased. The downregulation of KCNE1 and KCNB2 levels was greater when miR-1 was further upregulated through in vivo lentiviral infection. Electrophysiological tests indicated a shorter AERP, a great increase in the IKs and a higher atrial fibrillation inducibility. In addition, similar results were found when the levels of KCNE1 and KCNB2 were downregulated by small interfering RNA while keeping miR-1 level unaltered. Conversely, knockdown of miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs. KCNE1 and KCNB2 as the target genes for miR-1 were confirmed by luciferase activity assay.
  
  
  CONCLUSIONS
  These results indicate that miR-1 accelerates right atrial tachypacing-induced AERP shortening by targeting potassium channel genes, which further suggests that miR-1 plays an important role in the electrical remodeling of atrial fibrillation and exhibits significant clinical relevance as a potential therapeutic target for atrial fibrillation.
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Weizong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Zhongsu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Jiangrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051669:Shab Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D051669:Shab Potassium Channels