Connexin gene transfer preserves conduction velocity and prevents atrial fibrillation.
Connexin gene transfer preserves conduction velocity and prevents atrial fibrillation.
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DOI：
10.1161/circulationaha.111.053272
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发表时间：
2012-01-17
期刊：
影响因子：
37.8
通讯作者：
Donahue JK
中科院分区：
文献类型：
--
作者：
Igarashi T;Finet JE;Takeuchi A;Fujino Y;Strom M;Greener ID;Rosenbaum DS;Donahue JK
一些证据表明，房颤（AF）的维持依赖于再入机制。维持再入需要足够短的不应期和/或传导延迟，房颤与这两种改变有关。房颤发生纤维化、细胞功能障碍和间隙连接蛋白改变，导致传导延迟。我们进行这项研究是为了验证间隙连接蛋白过表达可以改善传导和预防房颤的假设。30头约克郡猪随机分为2组（窦性心律（SR）和房颤），每组又分为3个亚组：假手术对照组、表达连接蛋白（Cx） 40和Cx43的腺病毒基因治疗组（每个亚组n=5）。所有动物均有心外膜基因彩绘；房颤组有爆发性心房起搏。所有动物在基因转移后7天进行终末研究。SR动物有较强的转基因表达，但心房传导无变化。在房颤动物中，对照组Cx43表达减少和偏侧，Cx43基因转移使表达和细胞定位恢复到SR控制水平。与对照组相比，在房颤组中，Cx40和Cx43基因的转移改善了传导，减少了房颤。连接蛋白基因治疗可保持心房传导，预防房颤。
Several lines of evidence have suggested that maintenance of atrial fibrillation (AF) depends on reentrant mechanisms. Maintenance of reentry necessitates a sufficiently short refractory period and/or delayed conduction, and AF has been associated with both alterations. Fibrosis, cellular dysfunction and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF. Thirty Yorkshire swine were randomized into 2 groups (sinus rhythm (SR) and AF), and within each group into 3 subgroups: sham-operated control, gene therapy with adenovirus expressing connexin (Cx) 40 and Cx43 (n=5 per subgroup). All animals had epicardial gene painting; the AF group had burst atrial pacing. All animals underwent terminal study 7 days after gene transfer. SR animals had strong transgene expression but no atrial conduction changes. In AF animals, controls had reduced and lateralized Cx43 expression, and Cx43 gene transfer restored expression and cellular location to SR control levels. In the AF group, both Cx40 and Cx43 gene transfer improved conduction and reduced AF relative to controls. Connexin gene therapy preserved atrial conduction and prevented AF.