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Role of coxsackievirus and adenovirus receptor in the pathogenesis of dilated cardiomyopathy and its influencing factor

ISSN号：0366-6999
期刊名称：《中华医学杂志：英文版》
时间：0
分类：R541[医药卫生—心血管疾病;医药卫生—临床医学;医药卫生—内科学]
作者机构：[1]Department of Cardiology, Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China, [2]College of Bioinformatics Science and Technology, and Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State, Harbin Medical University, Harbin, Heilongjiang 150081, China
相关基金：This work was supported in part by the National High Tech Development Project of China, the 863 Program （No. 2007AA02Z329）, the National Natural Science Foundation of China （No. 30370798, 30571034, and 30570424） and the Key Project of Heilongjiang Province （No. GB07C32402）

作者： ZHANG Shuo[1], JIA Hai-bo[1], GONG Bin-sheng[2], ZHANG Shao-jun[2], LI Xia[2], YU Bo[1]

关键词：发病机理, 心机病, 蛋白质, 交互作用, 病例研究, dilated cardiomyopathy, viral receptor, protein interaction, gene cluster, bicluster

中文摘要：

背景尽管为心失败和突然的死亡的临床的处理在最后几十年被改进了，扩大心肌症(DCM ) 的病态和死亡增加了。导致 DCM 的内在的分子的事件的更好的理解因此是迫切的。坚持的病毒的感染(在病毒的心肌炎和 DCM 的心肌层的特别 coxsackievirus 组 B <,3>) 从来没被专家忽视过。最近的数据显示在病毒的心肌症的 coxsackievirus 和侵入人体气管粘膜的病菌受体(汽车) 的起来规定在这疾病的致病作为一个关键因素贡献病毒的感染。这研究试图由我们识别了的生物信息的 method.Methods 在 DCM 调查角色和汽车的规章的机制基因的簇由基于 DCM 的公共可得到的 microarray 数据集聚类算法与汽车共同表示(Kittleson，等。 2005 )，并且印射这些基因进蛋白质蛋白质相互作用网络在证实样品被基因的簇描绘在以后在蛋白质水平调查相互作用关系到对方正确地 partitioning.Results 与类似的表达式 pattem 包括汽车包含 33 基因的基因簇 GENESET 11 被簇算法识别，哪个 19 基因被发现有他们编码为当前的人的 pr 的蛋白质的相互作用信息特别，当在蛋白质水平的批评节点(叫的中心节点)涉及精力新陈代谢， 12 基因介绍，信号 transduction ，病毒的感染，免疫反应，房间 apoptosis ，房间增长，织物修理，在和汽车的 GENESET 11 的基因可以玩的 etc.Conclusions 在 DCM 的发展的一个病原的角色，主要在精力新陈代谢，信号 transduction ，病毒的感染，免疫反应，房间 apoptosis 和织物修理的机制包含了。

英文摘要：

Background Although clinical treatment for heart failure and sudden death has been improved over the last few decades, the morbidity and mortality of dilated cardiomyopathy （DCM） have increased. So a better understanding of the underlying molecular events leading to DCM is urgent. Persistent viral infection （especially coxsackievirus group B3） of the myocardium in viral myocarditis and DCM has never been neglected by experts. Recent data indicate that the up-regulation of coxsackievirus and adenovirus receptor （CAR） in viral cardiomyopathy contributes to viral infection as a key factor in the pathogenesis of this disease. This study aimed to investigate the role and regulatory mechanism of CAR in DCM by the bioinformatic method. Methods We identified the clusters of genes co-expressed with CAR by clustering algorithm based on the public available microarray dataset of DCM （Kittleson, et al. 2005）, and mapped these genes into the protein-protein interaction networks to investigate the interaction relationship to each other at the protein level after confirming that the samples are characterized by the cluster of genes in correctly partitioning. Results The gene cluster GENESET 11 containing 33 genes including CAR with similar expression pattern was identified by cluster algorithm, of which 19 genes were found to have interaction information of the protein encoded by them in the current human protein interaction database. Especially, 12 genes present as critical nodes （called HUB node） at the protein level are involved in energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis, cell proliferation, tissue repair, etc. Conclusions The genes in GENESET 11 together with CAR may play a pathogenic role in the development of DCM, mainly involved in the mechanism of energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis and tissue repair.

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