title: Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease.
abstract: BACKGROUND
  Extracellular matrix degradation is a sentinel pathologic feature of abdominal aortic aneurysm (AAA) disease. Diabetes mellitus, a negative risk factor for AAA, may impair aneurysm progression through its influence on the fibrinolytic system. We hypothesize that hyperglycemia limits AAA progression through effects on endogenous plasminogen activator inhibitor-1 (PAI-1) levels and subsequent reductions in plasmin generation.
  
  
  METHODS
  Experimental AAAs were induced in diabetic and control mice via the intra-aortic elastase infusion method. Serial transabdominal high-frequency ultrasound examinations were performed to monitor aortic diameter following elastase infusion. Circulating PAI-1 and plasmin alpha2-antiplasmin (PAP) complex concentrations were determined by ELISA and local expression of PAI-1 levels was examined by RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Hyperglycemia was associated with reduced AAA diameter, increased plasma PAI-1 concentration and reduced plasmin generation. Aneurysmal aortic PAI-1 gene expression increased in parallel with plasma concentration, with peak expression occurring early after aneurysm initiation.
  
  
  CONCLUSIONS
  Hyperglycemia increases PAI-1 expression and attenuates AAA diameter in experimental AAA disease. These results emphasize the role of the fibrinolytic pathway in AAA pathophysiology, and suggest a candidate mechanism for hyperglycemic inhibition of AAA disease.
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Dua
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Miyama
authors.forename: Junya
authors.initials: J
authors.lastname: Azuma
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Schultz
authors.forename: Mien
authors.initials: M
authors.lastname: Sho
authors.forename: John
authors.initials: J
authors.lastname: Morser
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dalman
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000150:complications* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D037502:Galectin 3 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications*; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012307:Risk Factors; D058258:Serpin E2; D015843:Serpins / Q000097:blood* / Q000235:genetics; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D037502:Galectin 3; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D005341:Fibrinolysin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse