| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Mitunobu Tohoku Univ., Graduate School of Medicine, Associate Professor (30282073)
WATANABE Tetsuo Tohoku Univ., Hospital, Research Associate (50291266)
GOTO Hitoshi Tohoku Univ., Hospital, Research Associate (00400333)
MIYAMA Noriyuki Tohoku Univ., Hospital, medical staff (80451566)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Objective: Basic fibroblast growth factor (bFGF) promotes the proliferation of vascular smooth muscle cell (SMC), and thus, it may inhibit the progression of an abdominal aortic aneurysm (AAA). We investigated the effects of bFGF incorporated into a gelatin sponge sheet (GSS), which could prolong the effects of bFGF, on an experimental AAA.
Methods: Experimental AAAs were induced in male Sprague-Dawley rats by infra-aortic elastase infusion. The rats were divided into three groups according to the treatments: 1) untreated control, 2) GSS alone, 3) GSS containing 100 ng of bFGF protein (bFGF+GSS). GSS was placed over the aorta after elastase infusion. We evaluated the aortic diameter at 14 postoperative days (POD) and the rupture rate of the aorta, and the aorta was harvested at POD 14 for pathological and transcriptional examination.
Result: Elastase infusion for 60 minutes markedly enlarged the aortic diameter from 1.58 0.06 mm to 7.74 f 1.97 mm in the untreated controls. However, such
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an enlargement of the aorta significantly decreased in both GSS alone and bFGF+GSS to 4.93 1.38 mm and. 4.39 0.92 mm, respectively. The pathological findings revealed a marked reduction of the elastic fibers and SMCs in the untreated controls, whereas the rats with bFGF+GSS significantly attenuated such a reduction in them. The rats with GSS alone showed less of a reduction, although no statistical difference was noted between the rats with GSS alone and the untreated controls. Immunostaining revealed an increase of positive cells for endogenous TGF b and bFGF in both GSS alone and bFGF+GSS. The transcript signals for matrix metalloproteinase-9 (MMP-9) significantly decreased in bFGF+GSS in comparison to those in untreated control or GSS alone. Elastase infusion for 75 minutes induced an aortic rupture in 50% of the rats without any treatment, in 38% of the rats with GSS alone, and in 22% of the rats with bFGF+GSS.
Conclusion: We noted the therapeutic effects on experimental AAA progression not only in bFGF+GSS, but also in GSS alone. GSS may have a therapeutic effect by the production of endogenous growth factors possibly induced by degradation of GSS, besides the dynamic effect of external wrapping. bFGF may proliferate SMCs, while suppressing the expression of MMP-9 possibly leading to a conservation of elastic fibers, which might result in a lower incidence of aortic rupture. Our present study suggests the potential usefulness of this novel therapy which may inhibit the progression of AAA. Less
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