Intraluminal Thrombus Enhances Proteolysis in Abdominal Aortic Aneurysms

Abstract

This study examined whether intraluminal thrombus in abdominal aortic aneurysms (AAAs) is a source of fibrinolytic activity and proteolysis that could weaken the aneurysm wall. Plasmin, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activity, plasminogen activator inhibitor 1 (PAI-1), and α2-antiplasmin (α2AP) antigen were measured in the AAA wall and juxtamural and luminal aspects of intraluminal thrombus in 18 patients. The aneurysm wall contained 100-fold higher tPA activity (1.06 ± 0.34 [standard error of measurement] U/mg soluble protein) compared with juxtamural thrombus (JMT) (0.011 ± 0.001 ) and luminal thrombus (LT) (0.01 ± 0.001) ( p < .00001) and over 6-fold higher uPA activity (29.3 ± 3.4 IU/mg compared with the JMT (4.3 ± 2.4, p = .00024) and LT (7.9 ± 1.76, p = .0005). The LT had significantly lower levels of PAI-1 (1.26 ± 0.34 ng/mg) than the AAA wall (2.08 ± 0.51, p = .04) and the JMT (3.94 ± 0.85, p = .007). The levels of α2AP in the wall (19.4 ± 3.1 ng/mg) were lower than in the JMT or LT (43.0 ± 7.9 ng/mg, p = .013, and 47.6 ± 6.0 ng/mg, p = .002, respectively). There was no significant difference, however, in plasmin activity among the AAA wall, JMT, and LT. There were significant amounts of latent gelatinase B (matrix metalloproteinase [MMP]-9) in the AAA, JMT, and LT. Mean levels of activated MMP-9 activity were similar in the AAA, JMT, and LT. Plasmin activation of MMPs at the interface between intraluminal thrombus and the aneurysm wall may enhance proteolysis and accelerate aneurysm expansion.