Open AccessLong Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
Author(s) -
Long QingQing,
Wang Hao,
Gao Wei,
Fan Yi,
Li YaFei,
Ma Yao,
Yang Yang,
Shi HaoJie,
Chen BingRui,
Meng HaoYu,
Wang QiMing,
Wang Fang,
Wang ZeMu,
Wang LianSheng
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005965
Subject(s) - medicine , heart failure , cardiology , downregulation and upregulation , gene knockdown , in vivo , biology , cell culture , biochemistry , genetics , microbiology and biotechnology , gene
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 ( I K s ) in CHF leads to action potential ( AP ) prolongation, and the I K 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 I Ks and prolonged AP s 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 Ks , 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 Ks and the prolongation of AP s 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 I K s , prolonged AP s, 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 .