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

Monica M. Dua, Noriyuki Miyama, Junya Azuma, Geoffrey M. Schultz, Mien Sho, John Morser, Ronald L. Dalman

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    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 α2-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.

    Original languageEnglish
    Pages (from-to)429-435
    Number of pages7
    JournalSurgery
    Volume148
    Issue number2
    DOIs
    Publication statusPublished - 2010 Jun 21

    ASJC Scopus subject areas

    • Surgery

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