title: Plasminogen activator and plasminogen activator inhibitor expression by normal and aneurysmal human aortic smooth muscle cells in culture.
abstract: OBJECTIVE
  Matrix metalloproteinases may play a major role in aortic wall degeneration causing abdominal aortic aneurysm (AAA). Available plasmin, required for MMP zymogen activation, is regulated by plasminogen activators (uPA, tPA) and plasminogen activator inhibitors (PAI-1, PAI-2). To appraise the impact of these regulatory proteins on aortic wall degeneration, expression at the level of translation and transcription was determined in human aortic smooth muscle cell (SMC) cultures.
  
  
  METHODS
  Explants were derived from aneurysmal aortic tissue (n = 6) and from three male organ donors. Cells were also stimulated with 0.1-1.0 ng/ml IL-1 beta.
  
  
  RESULTS
  uPA antigen and tPA antigen in the conditioned medium (CM) of normal SMCs were not detectable but AAA SMCs produced uPA (values are given as median (interquartile range)), [1.97 ng/ml/10(6) cells (1.50-8.21)] and tPA [7.02 ng/ml/10(6) cells (6.20-14.90)]. uPA antigen was absent from normal SMC cell extract (CE) but present in small amounts in AAA SMC CE [0.80 ng/mg protein (0.40-1.24)]. tPA was detectable in the CE of normal SMCs [3.2 ng/mg protein (1.90-3.40)] but at a lower concentration than in AAA SMCs [13.14 ng/mg protein (7.20-27.00)] (p < 0.05). IL-1 beta suppressed production of uPA and tPA in both types of SMCs. The difference in baseline PAI-1 release from normal SMCs and AAA SMCs was not statistically significant. Selective upregulation of PAI-1 was observed for AAA SMC after IL-1 beta stimulation. Northern analysis of AAA SMCs grown in serum containing medium exhibited clear bands for uPA.
  
  
  CONCLUSIONS
  Human AAA SMCs are a source of elevated plasminogen activators. In the absence of a reciprocal rise of PAI an imbalance is created favouring proteolysis.
authors.affiliation: Department of Surgery, Northwestern University Medical School, Chicago, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Louwrens
authors.forename: H C
authors.initials: HC
authors.lastname: Kwaan
authors.forename: W H
authors.initials: WH
authors.lastname: Pearce
authors.forename: J S
authors.initials: JS
authors.lastname: Yao
authors.forename: E
authors.initials: E
authors.lastname: Verrusio
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000166:cytology / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010960:Plasminogen Activators / Q000032:analysis*; D015849:Plasminogen Inactivators / Q000032:analysis*; D012016:Reference Values; D018709:Statistics, Nonparametric
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D015849:Plasminogen Inactivators; D010960:Plasminogen Activators