Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide.
Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide.
复制标题
在愈合犬梗死的心外膜边界区域的间隙连接重塑的表征以及Rotigaptide部分逆转的电生理效应。
DOI：
10.1161/circep.110.959312
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Duffy HS
中科院分区：
文献类型：
--
作者：
Macia E;Dolmatova E;Cabo C;Sosinsky AZ;Dun W;Coromilas J;Ciaccio EJ;Boyden PA;Wit AL;Duffy HS
愈合心肌梗死的边界区是致心律失常的底物，部分原因是心室间隙连接蛋白Connexin43 （Cx43）的结构和功能重塑。致心律失常底物中的Cx43是抗心律失常治疗的潜在靶点。我们在冠状动脉闭塞后5天，观察了愈合的犬梗死心外膜边界带（EBZ）的Cx43重构，并检测了间隙连接特异性药物罗替加肽是否可以逆转这种重构。EBZ中Cx43重塑的特征是Cx43蛋白减少、侧化和丝氨酸(S) 368位点Cx43磷酸化增加。罗替加肽部分逆转了Cx43的缺失，但不影响S368磷酸化的增加，也不逆转Cx43的侧化。罗替加肽不能阻止EBZ传导减慢，也不能减少程序性刺激诱导的持续性室性心动过速（SMVT），尽管它能减少EBZ有效不应期（ERP）。我们的结论是，愈合梗死边界区部分逆转Cx43重构可能不足以恢复正常传导或预防心律失常。
The border zone of healing myocardial infarcts is an arrhythmogenic substrate partly due to structural and functional remodeling of the ventricular gap junction protein, Connexin43 (Cx43). Cx43 in arrhythmogenic substrates is a potential target for antiarrhythmic therapy. We characterized Cx43 remodeling in the epicardial border zone (EBZ) of healing canine infarcts, 5 days after coronary occlusion and examined whether the gap junction specific agent, Rotigaptide, could reverse it. Cx43 remodeling in the EBZ was characterized by a decrease in Cx43 protein, lateralization and increased Cx43 phosphorylation at serine (S) 368. Rotigaptide partially reversed the loss of Cx43 but did not affect the increase in S368 phosphorylation nor did it reverse Cx43 lateralization. Rotigaptide did not prevent conduction slowing in EBZ nor did it decrease the induction of sustained ventricular tachycardia (SMVT) by programmed stimulation, although it did decrease the EBZ effective refractory period (ERP). We conclude that partial reversal of Cx43 remodeling in healing infarct border zone may not be sufficient to restore normal conduction or prevent arrhythmias.