Yonago Acta medica 2001;44:25–35
Expression of MMP-2, MMP-9 and TIMP-1 in the Wall of Abdominal Aortic Aneurysms
Kengo Nishimura, Shigetsugu Ohgi and Eiji Nanba*
Second Department of Surgery, Faculty of Medicine, Tottori University and *Gene Research
Center, Tottori University, Yonago 683-0826 Japan
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 (3045 mm), 17
with medium-large-diameter AAAs (> 45 mm) and 11 controls (1725 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.
Key words: abdominal aortic aneurysm; competitive polymerase chain reaction; immunohistochemistry; matrix metalloproteinase; tissue inhibitor of metalloproteinase
