title: Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery.
abstract: 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.
  
  
  CONCLUSIONS
  These results indicate that alterations in Cd44 expression mediate inflammation through a complex transcriptional network involving a number of previously uncharacterized genes.
authors.forename: Jody
authors.initials: J
authors.lastname: Albright
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Quizon
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, 500 Laureate Way, Suite 2303, Kannapolis, NC 28081, USA. bennettb@email.unc.edu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics*; D016122:Brachiocephalic Trunk / Q000378:metabolism*; D019295:Computational Biology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger