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Long noncoding RNA Kcna2 antisense RNA contributes to ventricular arrhythmias via silencing Kcna2 in rats with congestive heart failure
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نویسنده
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long q.-q. ,wang h. ,gao w. ,fan y. ,li y.-f. ,ma y. ,yang y. ,shi h.-j. ,chen b.-r. ,meng h.-y. ,wang q.-m. ,wang f. ,wang z.-m. ,wang l.-s.
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منبع
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journal of the american heart association - 2017 - دوره : 6 - شماره : 12
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چکیده
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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 (iks) in chf leads to action potential (ap) prolongation,and the iks 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 iks,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. © 2017 the authors.
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کلیدواژه
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IKs; Kcna2 antisense RNA; Long noncoding RNA; QTc; Ventricular arrhythmias
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آدرس
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departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments 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, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of emergency and intensive care,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China, departments of cardiology,the first affiliated hospital of nanjing medical university,nanjing, China
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Authors
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