title: 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 alpha2-antiplasmin (alpha2AP) 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 alpha2AP 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.
authors.affiliation: Academic Department of Surgery, King's College London, St Thomas' Hospital, London, United Kingdom. Tom.Carrell@gstt.nhs.uk
authors.forename: Tom W G
authors.initials: TW
authors.lastname: Carrell
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Burnand
authors.forename: Nuala A
authors.initials: NA
authors.lastname: Booth
authors.forename: Julia
authors.initials: J
authors.lastname: Humphries
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D005341:Fibrinolysin / Q000032:analysis; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D013927:Thrombosis / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis; D000979:alpha-2-Antiplasmin / Q000032:analysis
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator