Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts
Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts
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DOI：
10.1007/s00439-006-0193-2
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发表时间：
2006-08-01
期刊：
影响因子：
5.3
通讯作者：
Kittleson, Mark D.
中科院分区：
文献类型：
--
作者：
Meurs, Kathryn M.;Lacombe, Veronique A.;Kittleson, Mark D.
致心律失常性右心室心肌病（ARVC）是一种以室性快速性心律失常和纤维脂肪浸润为特征的心肌病，被认为优先影响右心室。心脏兰尼碱受体（RyR 2）基因突变已在一些具有独特形式ARVC（ARVC 2）的人类家族中被鉴定。虽然RyR 2在心室兴奋-收缩偶联中具有重要意义，但其编码基因的突变似乎对ARVC 2的右心室影响最大。应用免疫印迹和真实的时间PCR技术，对正常犬和ARVC犬的右心室、左心室和室间隔中RyR 2蛋白和信使RNA的表达进行了研究。RyR 2在正常心脏各室壁的表达均存在差异，右室表达最低（P < 0.05）。在ARVC犬模型的所有腔室中，RyR 2的信息和蛋白表达均降低。我们认为，右心室对ARVC的易感性增加可能与正常右心室中RyR 2的基线蛋白浓度低于左心室和室间隔相关，并且在这种ARVC犬模型中，所有三个区域均受到同等影响。使用这种自然发生的犬ARVC模型，我们可能对这种心肌病的发病机制提供了新的见解。
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of cardiomyopathy characterized by ventricular tachyarrhythmias and a fibrofatty infiltrate that is believed to preferentially affect the right ventricle. Mutations in the cardiac ryanodine receptor (RyR2) gene have been identified in some human families with a unique form of ARVC, ARVC2. Although the RyR2 has significant importance in excitation-contraction coupling across the ventricles, mutations in the gene encoding for it appear to have the greatest impact on the right ventricle in ARVC2. Using a canine model (boxer), the RyR2 protein and message RNA in the right ventricle, left ventricle and interventricular septum from normal dogs and dogs with ARVC were investigated by immunoblotting and real time PCR. The cardiac RyR2 message and protein expression were differentially expressed across the cardiac walls in the normal heart, with the lowest concentration expressed in the right ventricle (P < 0.05). The message and protein expression of the RyR2 were reduced in all chambers in the canine model of ARVC. We propose that the increased susceptibility of the right ventricle to ARVC may be associated with the lower baseline protein concentration of RyR2 in the normal right ventricle compared to the left ventricle and interventricular septum and that all three areas are equally affected in this canine model of ARVC. Using this naturally occurring model of canine ARVC, we may have provided new insights into the pathogenesis of this cardiomyopathy.