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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |