Relationship of matrix metalloproteinases 2 and 9 in the wall of abdominal aortic aneurysms

Abstract

This study examines the pathogenesis of abdominal aortic aneurysms (AAAs) with respect to pathological characteristics and expressions of matrix metalloproteinases (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1, in Tottori University Hospital, Japan. Thirty-four consecutive patients were operated on for (AAAs). During surgery, the anterior wall of the aneurysmal aorta was resected from the site of maximal diameter throughout the wall. AAA specimens consisted of the aneurysmal aortas, while control specimens consisted of the undulated aortas of autopsy cases. The expression of MMP-2, MMP-9 and TIMP-1 was evaluated by immunohistochemistry, Western blotting and competitive polymerase chain reaction (C-PCR). Immunohistochemistry showed MMP-2-positive cells and TIMP-1 positive cells mainly in the intima, and MMP-9-positive cells in the intima and adventitia. Western blotting revealed the expression of MMPs and TIMP-l variably in all the cases examined. C-PCR showed significantly higher elevation of MMP-2 mRNA in the small-diameter AAAs (30–45 mm), plus higher MMP-9 mRNA expression in both the small-diameter and the medium-large-diameter AAAs (45 < mm), than in controls. The ratio of MMP-2 to TIMP-1 mRNA levels in the small-diameter AAAs, and the ratio of MMP-9 to TIMP-1 mRNA levels in both the small-diameter and medium-large-diameter AAAs were significantly higher than in controls. The mRNA levels were significantly correlated between MMP-2 and MMP-9, between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1 in the AAAs. This study demonstrates that increases in mRNA imbalanced expression of MMPs/TIMP, as well as increases of MMP-2 and MMP-9 expression, may play crucial roles in the development and growth of AAAs, and TIMP-1 may play an important rule of preventing the aortic expansion.