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

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 hypoglycemia twins 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 Ham-aortic elastase infusion method. Serial transabdominal high-frequency ultrasound examinations were performed to monitor aortic diameter following elastase infusion. Circulating PAI-1 and plasma alpha 2-antiplasmin (PAP) complex concentrations were determined by ELISA and local expression of PAI-1 levels was examined by RTPCR 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 pea expression occurring early after aneurysm. initiation. Conclusion. Hypoglycemia increases PAI-1 expression and attenuates AAA diameter in experimental AAA disease These results emphasize the role al the fibrinolytic pathway in AAA pathophysiology, and suggest a candidate mechanism for hyperglycemic inhibition of AAA disease (Surgery 2010,148 429-35)