| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
An impaired mechanism of regulatory feedback by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) has been implicated in the development of abdominal aortic aneurysms (AAAs). This study was designed as basic research to establish a therapy for AAAs.
In 1998, the production of MMPs and TIMP-1 in the tissue culture of human AAA walls was examined. The production of MMP-1 and MMP-9 were significantly higher in the AAA group than in the control. The production of TIMP-1 was higher in the AAA group than in the control. The study also examined the effect of Doxycycline which was thought to be an inhibitor of MMPs. The production of MMP-9 was significantly lower in the Doxycycline group than in the control. However, the production of TIMP-1 was not lower in the Doxycycline group than in the control. These results indicated that Doxycycline inhibits MMPs regardless of TAMP-1.
In 1999 and 2000, the pathogenesis of AAAs was examined with respect to expressions of MMP-2, MMP-9 and TIMP-1. An aorta with a diameter between 30mm and 45mm was defined as a small-diameter AAA, and that with a diameter over 45mm as a medium-large-diameter AAA.Competitve PCR and Western blotting showed significantly higher elevation of MMP-2 in the small-diameter AAAs, plus higher MMP-9 expression in both the small-diameter and the medium-large-diameter AAAs, compared to the respective levels in controls. The mRNA levels were significantly correlated between TIMP-1 and MMP-9, and between MMP-2 and MMP-9 in AAAs, especially in medium-large-diameter AAAs. These results indicated that MMP-2 and MMP-9 may act cooperatively playing a crucial role in the development of AAAs, and that TIMP-1 inhibits MMP-9 in AAAs, especially in medium-large-diameter AAAs.
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