title: Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.
abstract: BACKGROUND
  The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.
  
  
  RESULTS
  We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).
  
  
  CONCLUSIONS
  Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Lillvis
authors.forename: Robert
authors.initials: R
authors.lastname: Erdman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Schworer
authors.forename: Alicia
authors.initials: A
authors.lastname: Golden
authors.forename: Kimberly
authors.initials: K
authors.lastname: Derr
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Laura A
authors.initials: LA
authors.lastname: Cox
authors.forename: Jianbin
authors.initials: J
authors.lastname: Shen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Vander Heide
authors.forename: Guy M
authors.initials: GM
authors.lastname: Lenk
authors.forename: Leigh
authors.initials: L
authors.lastname: Hlavaty
authors.forename: Li
authors.initials: L
authors.lastname: Li
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: David J
authors.initials: DJ
authors.lastname: Carey
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Lancaster
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D001012:Aorta, Abdominal / Q000254:growth & development / Q000378:metabolism; D001013:Aorta, Thoracic / Q000254:growth & development / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010215:Papio; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C073547:HOXA4 protein, human