Li Yao-Dong, Hong Yi-Fan, Yusufuaji Yueerguli, Tang Bao-Peng, Zhou Xian-Hui, Xu Guo-Jun, Li Jin-Xin, Sun Lin, Zhang Jiang-Hua, Xin Qiang, Xiong Jian, Ji Yu-Tong, Zhang Yu
Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.
Mol Med Rep. 2015 Sep;12(3):3243-3248. doi: 10.3892/mmr.2015.3831. Epub 2015 May 25.
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.
超极化激活的环核苷酸门控（HCN）阳离子通道介导心房的起搏电流。微小RNA（miR）家族miR-1和miR-133调节包括HCN通道在内的多个参与心肌功能的基因的表达。据推测，HCN2、HCN4、miR-1和miR-133表达的年龄依赖性变化可能与年龄相关的心房颤动有关，因此确定了成年（≤65岁）和老年患者（≥65岁）中这些表达水平与窦性心律之间的相关性。从60例接受冠状动脉旁路移植术的患者中采集右心耳样本。进行逆转录定量聚合酶链反应（PCR）和蛋白质印迹分析以确定靶RNA和蛋白质表达水平。与窦性心律的老年患者相比，心房颤动的老年患者表现出显著更高的HCN2和HCN4通道mRNA及蛋白质表达水平（P<0.05），但miR-1和miR-133的表达水平显著更低（P<0.05）。此外，与窦性心律的成年患者相比，窦性心律的老年患者表现出显著更高的HCN2和HCN4通道mRNA及蛋白质表达水平（P<0.05），但miR-1和miR-133的表达水平显著更低（P<0.05）。HCN2和HCN4的表达水平随年龄增加，与窦性心律的老年患者相比，年龄相关心房颤动患者的增加幅度更大。这些电生理变化可能有助于诱发触发心房颤动的异位早搏。
