Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

Abstract

Introduction: Rupture of an abdominal aortic aneurysm (AAA) is the cause of death in approximately 2% of men above 65 years. Most AAAs contain an intra-luminal thrombus (ILT), which is a potential source of proteases capable of degrading the underlying aneurysm wall. The AAA wall covered by a thick ILT shows more signs of matrix degradation compared to the wall free from ILT. The purpose of the present study was to evaluate the presence of protease activity in the ILT.

Materials and methods: ILT and peripheral blood from 32 patients undergoing elective surgery were collected. The ILT was divided into abluminal, luminal, and a middle layer in between. Collagenases, gelatinases, elastase, and their inhibitors were measured using ELISA in protein extracts from these layers. Immunohistochemistry was used for identification of cells.

Results: Neutrophil leukocytes and platelets were mostly detected in the luminal layer of the ILT. MMP-9 and neutrophil elastase were also abundant in this layer but with low activity. High concentrations of TIMP-1 and PAI-1 were detected in the abluminal layer, while alpha 1 antitrypsin was mostly found in the luminal layer of the ILT.

Conclusions: In AAA thick ILTs with multiple layers contain substantial amounts of proteases, but their activity is limited to the luminal layer. Proteases in the abluminal layer are mostly inactive, probably due to excess amounts of inhibitors and are consequently unable to directly participate in the pathogenesis of AAA.