title: Differential gene expression in coronary arteries from patients presenting with ischemic heart disease: further evidence for the inflammatory basis of atherosclerosis.
abstract: OBJECTIVE
  The pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques.
  
  
  RESULTS
  Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries (t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1beta [IL-1beta] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor-associated kinase [IRAK]). Differential expression of IL-1beta, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries.
  
  
  CONCLUSIONS
  These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.
authors.affiliation: Division of Clinical Sciences (North), University of Sheffield, Sheffield, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Satterthwaite
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Francis
authors.forename: Kim
authors.initials: K
authors.lastname: Suvarna
authors.forename: Stephen
authors.initials: S
authors.lastname: Blakemore
authors.forename: Chantelle
authors.initials: C
authors.lastname: Ward
authors.forename: Don
authors.initials: D
authors.lastname: Wallace
authors.forename: Martin
authors.initials: M
authors.lastname: Braddock
authors.forename: David
authors.initials: D
authors.lastname: Crossman
mesh_terms: D016000:Cluster Analysis; D003324:Coronary Artery Disease / Q000235:genetics* / Q000276:immunology; D003331:Coronary Vessels / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D017202:Myocardial Ischemia / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000235:genetics
chemical_list: D050800:STAT6 Transcription Factor