title: Effects of C-reactive protein on K(+) channel interaction protein 2 in cardiomyocytes.
abstract: Several studies have found that C-reactive protein (CRP) was associated with QTc interval prolongation and ventricular arrhythmia. However, little is known about the mechanisms involved. K(+) channel interaction protein 2 (KChIP2) is a necessary subunit for the formation of transient outward potassium current (Ito.f) which plays a critical role in early repolarization and QTc interval of heart. In this study, we aimed to evaluate the effects of CRP on KChIP2 and Ito.f in cardiomyocytes and to explore the potential mechanism. The neonatal mice ventricular cardiomyocytes were cultured and treated with CRP at different concentrations. The expression of KChIP2 was detected by real time quantitative PCR and Western blot. In addition, Ito.f current density was evaluated by whole cell patch clamp techniques. Our results showed that CRP significantly decreased the mRNA and protein expression of KChIP2 in time and doses dependent manners (P < 0.05), and also reduced the current density of Ito.f (P < 0.05). In addition, CRP increased the expression of NF-κB and decreased IκBα expression without significant influence on the expression of ERK1/2 and JNK. Meanwhile, the NF-κB inhibitor PDTC significantly attenuated the effects of CRP on KChIP2 and Ito.f current density. In conclusion, CRP could significantly down-regulate KChIP2 expression and reduce current density of Ito.f partly through NF-κB pathway, suggesting that CRP may directly or indirectly influence QTc interval and arrhythmia via influencing KChIP2 expression and Ito.f current density of cardiomyocytes.
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Jing-Ting
authors.initials: JT
authors.lastname: Mai
authors.affiliation: Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Wo-Liang
authors.initials: WL
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Nian-Sang
authors.initials: NS
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Fang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangzhou 510120, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120, China.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Chen
keywords: C-reactive protein; Ito.f current density; KChIP2; cardiomyocytes