on April 21, 2005
Published online before print April 21, 2005, doi: 10.1161/01.ATV.0000166601.49954.21
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Submitted on November 30, 2004
Accepted on April 6, 2005
Difference in Matrix-Degrading Protease Expression and Activity Between Thrombus-Free and Thrombus-Covered Wall of Abdominal Aortic Aneurysm
Monsur Kazi ;
From the Atherosclerosis Research Unit (M.K., C.Z., A.H., P.E.), King Gustav V Research Institute, Department of Medicine, Karolinska Institute; the Department of Vascular Surgery (M.K., J.S., U.H.), Karolinska Hospital, Karolinska Institute; St Görans Hospital (J.R.); and Cardiovascular Research, Center for Molecular Medicine (G.P.-B.), Karolinska Institute, Stockholm, Sweden.
* To whom correspondence should be addressed. E-mail: per.eriksson{at}medks.ki.se.
Objective--It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA rupture. Here, we examined the possibility that the intraluminal thrombus influences expression and activity of matrix-degrading proteases in the AAA wall.
Methods and Results--Twenty patients undergoing elective repair of AAAs were included. From each patient, specimens from both thrombus-covered and thrombus-free wall were taken for analysis. Gene arrays and quantitative real-time polymerase chain reaction showed that matrix metalloproteinase (MMP)-1, -7, -9, and -12 expressions were upregulated in the thrombus-free wall compared with the thrombus-covered wall. Immunohistochemistry confirmed the differential expression of MMP-9 but also localized MMP-9 to the interface between the thrombus and the underlying vessel wall. MMP-9 expression was colocalized with the presence of macrophages. Similar expression patterns were observed for urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1. Gelatinase activity was detected in the same regions as MMP-9 protein expression, ie, within the thrombus-free wall and in the interface between the thrombus and the underlying wall.
Conclusion--The present work demonstrates that protease expression and activity differs within the aneurysm wall. The source and activity of the proteases responsible for the degradation of the thrombus-covered wall need to be further determined.
Key words: abdominal aortic aneurysm • thrombus • gene expression • matrix metalloproteinases
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