title: Mouse strain-specific differences in vascular wall gene expression and their relationship to vascular disease.
abstract: OBJECTIVE
  Different strains of inbred mice exhibit different susceptibility to the development of atherosclerosis. The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice.
  
  
  RESULTS
  We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis.
  
  
  CONCLUSIONS
  Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study. To gain insights into the molecular pathways that are differentially activated in strains of mice with varied susceptibility to atherosclerosis, we performed comprehensive transcriptional profiling of their vascular wall. Genes identified through these studies expand the repertoire of factors in disease-related signaling pathways and identify novel candidate genes in atherosclerosis.
authors.affiliation: Donald W. Reynolds Cardiovascular Clinical Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. rtabibiazar@cvmed.stanford.edu <rtabibiazar@cvmed.stanford.edu>
authors.forename: Raymond
authors.initials: R
authors.lastname: Tabibiazar
authors.forename: Roger A
authors.initials: RA
authors.lastname: Wagner
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Spin
authors.forename: Euan A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Narasimhan
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Bradley
authors.initials: B
authors.lastname: Efron
authors.forename: Phil S
authors.initials: PS
authors.lastname: Tsao
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001025:Aortitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats