Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease

Surgery. 2010 Aug;148(2):429-35. doi: 10.1016/j.surg.2010.05.014. Epub 2010 Jun 19.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / blood*
  • Aortic Aneurysm, Abdominal / complications*
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / prevention & control
  • Disease Models, Animal
  • Fibrinolysin / metabolism
  • Fibrinolysis
  • Galectin 3 / metabolism
  • Gene Expression
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Risk Factors
  • Serpin E2
  • Serpins / blood*
  • Serpins / genetics
  • alpha-2-Antiplasmin / metabolism


  • Galectin 3
  • Serpin E2
  • Serpine2 protein, mouse
  • Serpins
  • alpha-2-Antiplasmin
  • plasmin-plasmin inhibitor complex
  • Fibrinolysin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse