Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure.
Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure.
复制标题
长非编码 RNA Kcna2 反义 RNA 通过沉默充血性心力衰竭大鼠的 Kcna2 导致室性心律失常
DOI：
10.1161/jaha.117.005965
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发表时间：
2017-12-20
影响因子：
5.4
通讯作者：
Wang LS
中科院分区：
文献类型：
--
作者：
Long QQ;Wang H;Gao W;Fan Y;Li YF;Ma Y;Yang Y;Shi HJ;Chen BR;Meng HY;Wang QM;Wang F;Wang ZM;Wang LS
背景充血性心力衰竭（CHF）是一种常见的心血管疾病，常伴有室性心律失常。 CHF中延迟整流钾电流（IK s）慢分量的减少导致动作电位（AP）延长，而IK s是室性心律失常发生的重要因素。然而，室性心律失常的分子机制仍不清楚。方法和结果使用定量实时逆转录聚合酶链反应和蛋白质印迹法测量大鼠心脏组织中的 Kcna2 和 Kcna2 反义 RNA (Kcna2 AS) 转录物表达。 CHF 大鼠左心室心肌中 Kcna2 mRNA 减少 43%。心脏中 Kcna2 的敲除降低了心肌细胞中的 IK 并延长了 AP，这与心力衰竭中观察到的变化一致。相反，Kcna2 在心脏中的过度表达显着减弱了 CHF 引起的 IK 下降、AP 延长和室性心律失常。在患有 CHF 和去氧肾上腺素诱导的心肌细胞肥大的大鼠中，Kcna2 AS 上调约 1.7 倍。 Kcna2 AS 抑制增加了 CHF 诱导的 Kcna2 下调。因此，根据心电图检测，Kcna2 AS 减轻了体内和体外 IK 的减少和 AP 的延长，并减少了室性心律失常。结论 CHF大鼠心室Kcna2 AS表达增加，沉默Kcna2可导致IK减少、AP延长以及室性心律失常的发生。因此，Kcna2 AS可能成为预防和治疗CHF患者室性心律失常的新靶点。
Background Congestive heart failure (CHF) is a common cardiovascular disease that is often accompanied by ventricular arrhythmias. The decrease of the slow component of the delayed rectifier potassium current (IK s) in CHF leads to action potential (AP) prolongation, and the IK s is an important contributor to the development of ventricular arrhythmias. However, the molecular mechanisms underlying ventricular arrhythmias are still unknown. Methods and Results Kcna2 and Kcna2 antisense RNA (Kcna2 AS) transcript expression was measured in rat cardiac tissues using quantitative real‐time reverse transcription–polymerase chain reaction and Western blotting. There was a 43% reduction in Kcna2 mRNA in the left ventricular myocardium of rats with CHF. Kcna2 knockdown in the heart decreased the IKs and prolonged APs in cardiomyocytes, consistent with the changes observed in heart failure. Conversely, Kcna2 overexpression in the heart significantly attenuated the CHF‐induced decreases in the IKs, AP prolongation, and ventricular arrhythmias. Kcna2 AS was upregulated ≈1.7‐fold in rats with CHF and with phenylephrine‐induced cardiomyocyte hypertrophy. Kcna2 AS inhibition increased the CHF‐induced downregulation of Kcna2. Consequently, Kcna2 AS mitigated the decrease in the IKs and the prolongation of APs in vivo and in vitro and reduced ventricular arrhythmias, as detected using electrocardiography. Conclusions Ventricular Kcna2 AS expression increases in rats with CHF and contributes to reduced IK s, prolonged APs, and the occurrence of ventricular arrhythmias by silencing Kcna2. Thus, Kcna2 AS may be a new target for the prevention and treatment of ventricular arrhythmias in patients with CHF.
影响因子：
5.5
作者：
Lee, Hsiang-Chun;Rudy, Yoram;Po-Yuan;Sheu, Sheng-Hsiung;Chang, Jan-Gowth;Cui, Jianmin
通讯作者：
Cui, Jianmin