Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Geriatrics, Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
J Am Heart Assoc. 2017 Dec 20;6(12):e005965. doi: 10.1161/JAHA.117.005965.
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 (I) in CHF leads to action potential (AP) prolongation, and the I is an important contributor to the development of ventricular arrhythmias. However, the molecular mechanisms underlying ventricular arrhythmias are still unknown.
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 I 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 I, 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 I and the prolongation of APs in vivo and in vitro and reduced ventricular arrhythmias, as detected using electrocardiography.
Ventricular Kcna2 AS expression increases in rats with CHF and contributes to reduced I, 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.
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 导致延迟整流钾电流（I）缓慢成分减少，引起动作电位（AP）延长，而 I 是室性心律失常发展的重要因素。然而，导致室性心律失常的分子机制尚不清楚。
采用实时定量逆转录聚合酶链反应和 Western blot 检测大鼠心脏组织中 Kcna2 和 Kcna2 反义 RNA（Kcna2 AS）转录物的表达。CHF 大鼠左心室心肌 Kcna2 mRNA 减少 43%。心脏中的 Kcna2 敲低可降低心肌细胞中的 I 和延长 AP，与心力衰竭中观察到的变化一致。相反，心脏中的 Kcna2 过表达可显著减弱 CHF 引起的 I 降低、AP 延长和室性心律失常。CHF 大鼠和苯肾上腺素诱导的心肌细胞肥大时，Kcna2 AS 上调约 1.7 倍。Kcna2 AS 抑制增加了 CHF 诱导的 Kcna2 下调。因此，Kcna2 AS 减轻了体内和体外 CHF 引起的 I 降低和 AP 延长，并减少了心电图检测到的室性心律失常。
CHF 大鼠心室 Kcna2 AS 表达增加，通过沉默 Kcna2 导致 I 降低、AP 延长和室性心律失常发生。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。
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