Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies
Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies
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DOI：
10.1093/eurheartj/ehl095
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发表时间：
2006-08-01
影响因子：
39.3
通讯作者：
Rampazzo, Alessandra
中科院分区：
文献类型：
--
作者：
Basso, Cristina;Czarnowska, Elzbieta;Rampazzo, Alessandra
目的致心律失常性右室心肌病(ARVC)的心肌超微结构特征迄今未见系统研究。最近发现的编码插入盘蛋白的基因突变促使我们对心内膜心肌活检进行了透射电子显微镜研究。方法与结果21例符合国际工作组诊断标准的ARVC先证者接受了右室心内膜心肌活检和桥粒(D)蛋白编码基因的筛选。对心肌细胞间盘进行了透射电子显微镜分析，并与10例对照组和10例特发性扩张型心肌病患者进行了比较。在ARVC活检标本中发现广泛的纤维脂肪替代，残余心肌占59+/-23%。检出致病性D基因突变10例(48%)，其中桥粒蛋白2突变4例，桥粒蛋白3例，嗜血小板蛋白2 3例。ARVC组间盘平均D长度和D百分比长度显著高于ARVC组，D数显著低于ARVC组，D间隙明显扩大。此外，75%的ARVC患者在间盘卷曲指数正常的情况下可发现D的异常位置，52%的ARVC患者存在异常的小连接，32%的ARVC患者存在乳头状内部斑块。结论ARVC患者间盘重构的超微结构证据，以及半数先证者D蛋白编码基因的阳性筛查，符合细胞间连接型心肌病。
Aims The ultrastructural features of the myocardium in arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been systematically investigated so far. The recent discovery of gene mutations encoding intercalated disc proteins prompted us to perform a transmission electron microscopy study on endomyocardial biopsies.Methods and results Twenty-one ARVC probands who fulfilled the international Task Force diagnostic criteria underwent right ventricular endomyocardial biopsy and screening of desmosome (D) protein encoding genes. Myocyte intercalated discs were analysed by transmission electron microscope and the data were compared with those of 10 controls and 10 patients with idiopathic dilated cardiomyopathy.Extensive fibro-fatty replacement with a residual myocardium of 59 +/- 23% was found in ARVC biopsy samples. Pathogenic D gene mutations were identified in 10 (48%): desmoglein-2 in four, desmoplakin in three and plakophilin-2 in three. Mean D length and D percent length of intercalated disc were significantly higher, D number was significantly lower and D gap was widened in ARVC. Moreover, abnormally located D in 75%, abnormal small junctions in 52%, and pate internal plaques in 32% of ARVC patients were found in the presence of a normal intercalated disc convolution index.Conclusion The ultrastructural evidence of intercalated discs remodelling in ARVC, together with the positive screening of D protein encoding genes in half of probands, are in keeping with an intercellular junction cardiomyopathy.