Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.
Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.
复制标题
年龄相关心房颤动患者中超极化激活的环核苷酸门控通道以及 microRNA-1 和 -133 的表达发生改变
DOI：
10.3892/mmr.2015.3831
复制
发表时间：
2015-09
影响因子：
3.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li YD;Hong YF;Yusufuaji Y;Tang BP;Zhou XH;Xu GJ;Li JX;Sun L;Zhang JH;Xin Q;Xiong J;Ji YT;Zhang Y
超极化激活的环核苷酸门控(HCN)阳离子通道介导心房起搏电流。MicroRNA(MiR)家族miR-1和miR-133调节多种参与心肌功能的基因的表达，包括HCN通道。推测HCN_2、HCN_4、miR-1和miR-133表达的年龄依赖性变化可能参与了年龄相关性房颤的发生，从而确定了成人(≤65岁)和老年患者(≥65岁)的表达水平与窦性心律之间的相关性。采集60例冠状动脉旁路移植术患者的右心耳标本。逆转录-定量聚合酶链式反应(PCR)和免疫印迹分析以确定目标RNA和蛋白质表达水平。与老年窦性心律患者相比，老年房颤患者HCN2和HCN4通道基因和蛋白表达水平显著升高(P<；0.05)，而miR-1和miR-133表达水平显著降低(P<；0.05)。此外，老年窦性心律患者与成人窦性心律患者相比，HCN2和HCN4通道基因的表达水平显著升高(P<；0.05)，miR-1和-133的表达水平显著降低(P<；0.05)。HCN_2和HCN_4的表达水平随年龄增长而升高，且年龄相关性心房颤动患者较陈旧性窦性心律患者升高更明显。这些电生理变化可能导致异位性早搏的诱发，从而触发房颤。
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.