Role of coxsackievirus and adenovirus receptor in the pathogenesis of dilated cardiomyopathy and its influencing factor.
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.
Zhang
Shuo
S
Department of Cardiology, Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Jia
Hai-Bo
HB
Gong
Bin-Sheng
BS
Zhang
Shao-Jun
SJ
Li
Xia
X
Yu
Bo
B
D002311:Cardiomyopathy, Dilated / Q000209:etiology*; D019295:Computational Biology; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006801:Humans; D005810:Multigene Family; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus