title: Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.
abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age‑dependent changes in HCN2, HCN4, miR‑1 and miR‑133 expression may contribute to age‑associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR‑1 and miR‑133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR‑1 and ‑133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age‑associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Yao-Dong
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Hong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Yueerguli
authors.initials: Y
authors.lastname: Yusufuaji
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Bao-Peng
authors.initials: BP
authors.lastname: Tang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Yu-Tong
authors.initials: YT
authors.lastname: Ji
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C578710:HCN2 protein, human; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D009124:Muscle Proteins; D015221:Potassium Channels; D012333:RNA, Messenger