Significance of intraluminal thrombus in abdominal aortic aneurysm

Most AAAs contain an intraluminal thrombus (ILT) and the volume of the ILT correlates with aneurysm size. The thrombus-covered wall is a common site for rupture after bleeding into the ILT.

The hypothesis for this thesis was generated when Kazi et al discovered differences in AAA wall between ILT covered and ILT free aortic wall. From computed tomography images of patients with abdominal aortic aneurysms containing an eccentric intraluminal thrombus, the aortic wall appeared to be partially in direct contact with the blood flow on one side, while the opposite aortic wall was covered by the ILT. In that study they concluded that the aorta portion situated under the ILT is thinner, with fragmented elastin fibers, apoptosis of smooth muscle cells and generally is more degraded compared to the AAA wall, which is not under the ILT. This characteristic difference was postulated to be due to mere presence of the ILT. In this thesis we investigated the role of the ILT in AAA by concentrating on the content of the ILT in terms of proteases and their activities and inhibitors.

We have collected ILT and AAA wall from 57 patients (14 women, 43 men) obtained during elective surgery and examined them by proteomic methods. We have found that MMP1-2-9, and13 and elastase and inhibitors, a-1 anti-trypsin, TIMP-1 and PAI-1 are present in the various layers of the ILT, but mostly active in the layer adjacent to blood flow. We also found significant amounts of MMP9 in complex with N-GAL in AAA tissue. Activity of MMP9 is preserved upon binding to N-GAL. Further, unpublished data show that membrane bound proteases are present and carried by microvesicles and are active in the ILT, particularly in the acellular layer of the ILT adjacent to the aortic wall.

In summary, ILT contains various active proteases. These proteases may contribute to degradation of the vessel wall and concomitantly lead to AAA rupture.

List of scientific papers

I. Presence of N-GAL/MMP-9 complexes in human abdominal aortic aneurysms. Folkesson M, Kazi M, Zhu C, Silveira A, Hemdahl AL, Hamsten A, Hedin U, Swedenborg J, Eriksson P. Thromb Haemost. 2007 Aug;98(2):427-33.
https://doi.org/10.1160/TH06-11-0638

II. Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms. Folkesson M, Silveira A, Eriksson P, Swedenborg J. Atherosclerosis. 2011 Oct;218(2):294-9. Epub 2011 May 11.
https://doi.org/10.1016/j.atherosclerosis.2011.05.002

III. Proteolytically Active ADAM10 and ADAM17 Carried on Membrane Microvesicles in Human Abdominal Aortic Aneurysms. Maggie Folkesson, Chunjun Li, Siw Frebelius , Jesper Swedenborg, Kevin Jon Williams, Joy Roy, Per Eriksson, and Ming-Lin Liu. [Manuscript]