文章基本信息

标题：Impaired N-cadherin-mediated adhesion increases the risk of inducible ventricular arrhythmias in isolated rat hearts
本地全文：下载
作者：Hong-jun Zhu ; Xiao-Mei Ding ; Jian-gang Zou 等
期刊名称：Scientific Research and Essays
印刷版ISSN：1992-2248
出版年度：2012
卷号：7
期号：33
页码：2983-2991
DOI：10.5897/SRE12.042
语种：English
出版社：Academic Journals
摘要：Recent studies suggest that cadherin-mediated adherens junctions may be impaired in diseases and pathologic processes related to ventricular arrhythmias, which are concomitant with decreased connexin 43 (Cx43). In this study, we evaluated the acute arrhythmogenic effects of adherens junction impairment in isolated rat hearts. A total of 56 hearts isolated from adult male rats were perfused with 0.2 mM AHAVD, a synthetic peptide that specifically inhibits N-cadherin (n = 18); 0.2 mM IPPINL, a nonsense peptidase that contains the highly conserved cadherin sequence (n = 18), and oxygenated Krebs–Henseleit buffer as the control (n = 20). Under programmed stimuli, ventricular tachyarrhythmias were induced more in the AHAVD-perfused hearts (9/18) than the IPPINL-perfused hearts (4/18) and those in the control (3/20) group (P < 0.05). The conduction velocity of the left ventricular myocardium exhibited an inverse pattern in these three groups (53.5 ± 6.3 cm/s, 65.2 ± 6.2 cm/s, and 66.3 ± 8.8 cm/s, respectively, P < 0.05). The effective refractory period and the epicardial action potential duration at 90% repolarization were not significantly different among the groups after 1 h of perfusion. Cx43 redistribution and PS368 decrease was observed in the AHAVD-perfused heart tissues. The reduction in functional GJs in the intercalated discs of cardiomyocytes may be one of the initial mechanisms by which myocardial conduction is blunted. Furthermore, rat hearts with impaired adherens junctions are more susceptible to ventricular tachyarrhythmias.
关键词：Adherens junctions; N-cadherin; connexin 43; pS368; Ventricular tachyarrhythmia