title: Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.
abstract: BACKGROUND
  Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA.
  
  
  METHODS
  Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression.
  
  
  RESULTS
  MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall.
  
  
  CONCLUSIONS
  The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.
authors.affiliation: Department of Vascular Surgery, St George's Hospital Medical School, London, UK.
authors.forename: W R W
authors.initials: WR
authors.lastname: Wilson
authors.forename: E C
authors.initials: EC
authors.lastname: Schwalbe
authors.forename: J L
authors.initials: JL
authors.lastname: Jones
authors.forename: P R F
authors.initials: PR
authors.lastname: Bell
authors.forename: M M
authors.initials: MM
authors.lastname: Thompson
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020784:Matrix Metalloproteinase 8