Expression of MMP-2, MMP-9 and TIMP-1 in the Wall of Abdominal Aortic Aneurysms

An impaired mechanism of regulatory feedback by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) has been implicated in the development of abdominal aortic aneurysms (AAAs). This study examined the pathogenesis of AAAs with respect to pathological characteristics and expressions of MMP-2, MMP-9 and TIMP-1. Their expressions were evaluated by immunohistochemistry, competitive polymerase chain reaction (PCR) and Western blotting in a total of 23 consecutive AAAs. The AAA specimens were obtained by surgery, while control specimens were obtained at autopsy. Specimens consisted of 6 patients with small-diameter AAAs (30?45 mm), 17 with medium-large-diameter AAAs (> 45 mm) and 11 controls (17?25 mm). Immunohistochemistry showed MMP-2- and TIMP-1-positive cells mainly in the intima, and MMP-9-positive cells in the intima and adventitia. Competitive PCR showed a significantly higher expression of MMP-2 messenger RNA (mRNA) in the small-diameter AAAs, and higher expressions of MMP-9 mRNA in the small-diameter and medium-large-diameter AAAs than in the controls. The mRNA levels significantly correlated between TIMP-1 and MMP-9, and between MMP-2 and MMP-9 in the AAAs, especially in the medium-large-diameter AAAs. Western blotting revealed the expression of MMPs and TIMP-1 variably in all the specimens examined. These results indicated that MMP-2 and MMP-9 might act cooperatively and play a crucial role in the development of AAAs, and that TIMP-1 inhibits MMP-9 in the AAAs, especially in those medium-large-diameter AAAs.