Structural and molecular pathology of the heart in Carvajal syndrome
Structural and molecular pathology of the heart in Carvajal syndrome
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DOI：
10.1016/s1054-8807(03)00107-8
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Saffitz, JE
中科院分区：
文献类型：
--
作者：
Kaplan, SR;Gard, JJ;Saffitz, JE
背景：Carvajal综合征是一种家族性心脏皮肤综合征，由羊毛状毛发、掌跖角化病和心脏病组成。它是由桥粒斑蛋白的隐性缺失突变引起的，桥粒斑蛋白是一种细胞内蛋白，将桥粒粘附分子连接到细胞骨架的中间丝。Carvajal综合征的病理尚未描述。方法：在这里，我们报告的结构和分子病理学的Carvajal综合征的心脏的第一个描述。我们的特点是大体和显微病理学，并确定了在心室肌的闰盘和中间丝蛋白的表达和分布的变化。结果如下：我们发现了一种独特的心肌病，其特征是心室肥大和扩张、局灶性心室动脉瘤以及闰盘明显的超微结构异常，但没有纤维脂肪浸润或心肌替代的证据。我们还观察到在闰盘上桥粒斑蛋白、斑珠蛋白和差距连接蛋白连接蛋白43的特异性免疫反应信号显著减少。中间丝蛋白，结蛋白，这是已知的结合desmoplakin，表现出正常的细胞内分布模式，但未能本地化在闰盘。结论：Carvajal综合征桥粒斑蛋白突变导致具有独特病理特征的心肌病。在Carvajal综合征中，闰盘处改变的蛋白质-蛋白质相互作用可能导致收缩和电功能障碍。(C)2004年爱思唯尔公司All rights reserved.
Background: Carvajal syndrome is a familial cardiocutaneous syndrome consisting of woolly hair, palmoplantar keratoderma, and heart disease. It is caused by a recessive deletion mutation in desmoplakin, an intracellular protein that links desmosomal adhesion molecules to intermediate filaments of the cytoskeleton. The pathology of Carvajal syndrome has not been described. Methods: Here, we report the first description of the structural and molecular pathology of the heart in Carvajal syndrome. We characterized gross and microscopic pathology and identified changes in expression and distribution of intercalated disk and intermediate filament proteins in ventricular myocardium. Results: We identified a unique cardiomyopathy characterized by ventricular hypertrophy and dilatation, focal ventricular aneurysms, and distinct ultrastructural abnormalities of intercalated disks, but no evidence of fibrofatty infiltration or replacement of myocardium. We also observed markedly decreased amounts of specific immunoreactive signal for desmoplakin, plakoglobin, and the gap junction protein, connexin43, at intercalated disks. The intermediate filament protein, desmin, which is known to bind desmoplakin, showed a normal intracellular pattern of distribution but failed to localize at intercalated disks. Conclusions: The desmoplakin mutation in Carvajal syndrome produces a cardiomyopathy with unique pathologic features. Altered protein-protein interactions at intercalated disks likely cause both contractile and electrical dysfunction in Carvajal syndrome. (C) 2004 Elsevier Inc. All rights reserved.