Cargando…

Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure

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 impo...

Descripción completa

Detalles Bibliográficos
Autores principales: Long, Qing‐Qing, Wang, Hao, Gao, Wei, Fan, Yi, Li, Ya‐Fei, Ma, Yao, Yang, Yang, Shi, Hao‐Jie, Chen, Bing‐Rui, Meng, Hao‐Yu, Wang, Qi‐Ming, Wang, Fang, Wang, Ze‐Mu, Wang, Lian‐Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778995/
https://www.ncbi.nlm.nih.gov/pubmed/29263036
http://dx.doi.org/10.1161/JAHA.117.005965
_version_ 1783294453711110144
author Long, Qing‐Qing
Wang, Hao
Gao, Wei
Fan, Yi
Li, Ya‐Fei
Ma, Yao
Yang, Yang
Shi, Hao‐Jie
Chen, Bing‐Rui
Meng, Hao‐Yu
Wang, Qi‐Ming
Wang, Fang
Wang, Ze‐Mu
Wang, Lian‐Sheng
author_facet Long, Qing‐Qing
Wang, Hao
Gao, Wei
Fan, Yi
Li, Ya‐Fei
Ma, Yao
Yang, Yang
Shi, Hao‐Jie
Chen, Bing‐Rui
Meng, Hao‐Yu
Wang, Qi‐Ming
Wang, Fang
Wang, Ze‐Mu
Wang, Lian‐Sheng
author_sort Long, Qing‐Qing
collection PubMed
description 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 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(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 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 I(K) (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.
format Online
Article
Text
id pubmed-5778995
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-57789952018-01-26 Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure Long, Qing‐Qing Wang, Hao Gao, Wei Fan, Yi Li, Ya‐Fei Ma, Yao Yang, Yang Shi, Hao‐Jie Chen, Bing‐Rui Meng, Hao‐Yu Wang, Qi‐Ming Wang, Fang Wang, Ze‐Mu Wang, Lian‐Sheng J Am Heart Assoc Original Research 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 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(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 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 I(K) (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. John Wiley and Sons Inc. 2017-12-20 /pmc/articles/PMC5778995/ /pubmed/29263036 http://dx.doi.org/10.1161/JAHA.117.005965 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Long, Qing‐Qing
Wang, Hao
Gao, Wei
Fan, Yi
Li, Ya‐Fei
Ma, Yao
Yang, Yang
Shi, Hao‐Jie
Chen, Bing‐Rui
Meng, Hao‐Yu
Wang, Qi‐Ming
Wang, Fang
Wang, Ze‐Mu
Wang, Lian‐Sheng
Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title_full Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title_fullStr Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title_full_unstemmed Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title_short Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
title_sort long noncoding rna kcna2 antisense rna contributes to ventricular arrhythmias via silencing kcna2 in rats with congestive heart failure
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778995/
https://www.ncbi.nlm.nih.gov/pubmed/29263036
http://dx.doi.org/10.1161/JAHA.117.005965
work_keys_str_mv AT longqingqing longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT wanghao longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT gaowei longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT fanyi longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT liyafei longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT mayao longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT yangyang longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT shihaojie longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT chenbingrui longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT menghaoyu longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT wangqiming longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT wangfang longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT wangzemu longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure
AT wangliansheng longnoncodingrnakcna2antisensernacontributestoventriculararrhythmiasviasilencingkcna2inratswithcongestiveheartfailure