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Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery
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Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery
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Journal Article
Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery
2014
Overview
Background
Atherosclerosis, the underlying cause of cardiovascular disease, results from both genetic and environmental factors.
Methods
In the current study we take a systems-based approach using weighted gene co-expression analysis to identify a candidate pathway of genes related to atherosclerosis. Bioinformatic analyses are performed to identify candidate genes and interactions and several novel genes are characterized using
in-vitro
studies.
Results
We identify 1 coexpression module associated with innominate artery atherosclerosis that is also enriched for inflammatory and macrophage gene signatures. Using a series of bioinformatics analysis, we further prioritize the genes in this pathway and identify
Cd44
as a critical mediator of the atherosclerosis. We validate our predictions generated by the network analysis using
Cd44
knockout mice.
Conclusion
These results indicate that alterations in
Cd44
expression mediate inflammation through a complex transcriptional network involving a number of previously uncharacterized genes.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
