title: Role of complement cascade in abdominal aortic aneurysms.
abstract: OBJECTIVE
  The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs).
  
  
  RESULTS
  Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues.
  
  
  CONCLUSIONS
  These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822-2610, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Hinterseher
authors.forename: Robert
authors.initials: R
authors.lastname: Erdman
authors.forename: Larry A
authors.initials: LA
authors.lastname: Donoso
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Vrabec
authors.forename: Charles M
authors.initials: CM
authors.lastname: Schworer
authors.forename: John H
authors.initials: JH
authors.lastname: Lillvis
authors.forename: Amy M
authors.initials: AM
authors.lastname: Boddy
authors.forename: Kimberly
authors.initials: K
authors.lastname: Derr
authors.forename: Alicia
authors.initials: A
authors.lastname: Golden
authors.forename: William D
authors.initials: WD
authors.lastname: Bowen
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Nikos
authors.initials: N
authors.lastname: Tapinos
authors.forename: James R
authors.initials: JR
authors.lastname: Elmore
authors.forename: David P
authors.initials: DP
authors.lastname: Franklin
authors.forename: John L
authors.initials: JL
authors.lastname: Gray
authors.forename: Robert P
authors.initials: RP
authors.lastname: Garvin
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Gerhard
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D016022:Case-Control Studies; D047369:Chromatin Immunoprecipitation; D003167:Complement Activation / Q000235:genetics; D003175:Complement C2 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D050799:STAT5 Transcription Factor / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D003175:Complement C2; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D003165:Complement System Proteins