Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts
Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts
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DOI：
10.1016/j.cardiores.2006.06.016
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发表时间：
2006-10-01
影响因子：
10.8
通讯作者：
Hatem, Stphane N.
中科院分区：
文献类型：
--
作者：
Rucker-Martin, Catherine;Milliez, Paul;Hatem, Stphane N.
目的：缝隙连接蛋白在包括房颤在内的多种心脏疾病中表达和分布异常，被认为有利于传导减慢和心律失常。在此，我们研究了心房结构重构在缝隙连接紊乱中的作用，以及重新分布的连接蛋白是否可以形成新的功能连接通道。方法：应用免疫印迹和免疫组织化学方法检测人右心房标本和心肌梗死后大鼠心房组织中连接蛋白-43(Cx43)的表达。结果：在慢性血流动力学超负荷的窦性心律的人心房和MI大鼠的扩张的心房中，Cx43被去磷酸化，并从间盘重新分布到侧细胞膜。MI组大鼠间盘间隙连接较小(减少20%)，Cx43含量极少(假手术组为42~98个)，Cx43为0或1个；在心肌细胞的侧膜中，可以观察到大量的连接蛋白聚集体，其中包含非磷酸化的Cx43。这些连接蛋白聚集体在任何情况下都没有组装成缝隙连接斑块状结构。而N-钙粘附素在间盘中有良好的组织。心肌梗死大鼠心房肌细胞-肌细胞偶联很少，无肌细胞-成纤维细胞偶联。心房重构的消退与Cx43定位的正常化有关。结论：心房心肌的结构改变是连接蛋白和缝隙连接紊乱的重要因素。此外，重新分布的Cx43不形成连接通道。(C)2006年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objectives: The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels.Methods: Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer.Results: In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or I gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization.Conclusion: Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.