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.
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.
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）
