| Co-Investigator(Kenkyū-buntansha) |
NANJO Hiroshi Akita University, School of Medicine, Lecturer, 医学部, 講師 (70250892)
KAWAMURA Koichi Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (00091801)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
High-flow rabbit common carotid arteries remodel as follows (mainly obtained from 2002-2003, but some findings included our previous findings).
1.Endothelial cells (ECs) start to proliferate at 1.25-day of high-flow, peaked at 2-day, still high at 3-day, and subside at 4-day
2.At 3-day of high-flow, ECs are going to contact with medial smooth muscle cells (SMCs) forming EC-SMC couplings.
3.From 3-day to 4-day, focal proliferation of SMCs occurs.
4.Internal elastic lamina gaps (IEL-gaps) start to appear at 4-day of high-flow.
5.Arterial lumen expands as IEL-gaps expand thereafter.
6.At 4-week of high-flow, when high-flow induced arterial remodeling happens, almost 50% lumen surface is IEL-gaps.
7.Returning to the normal flow by AVF closure, arterial lumen decreases, but the IEL-gaps are still wide and never disappear.
8.SMCs in media migrate into intima through IEL-gaps during flow-decrease induced arterial narrowing to induce intimal thickening (flow-alteration induced intimal thickening).
9.Flow-alteration induced intimal thickening occurs in each flow-alteration and it pile up progressively.
From 1 to 2, remarkable EC activation occurs with high MMP2, MMP9, MT-MMP, and TIMP. TGF-beta and VEGF increase. Ultrastructural observation revealed that activated ECs are similarly observed in both high-flow loaded arteries and high-flow capillaries. During the formation of EC-SMC couplings, there appear many abluminal cytoplasmic protrusions, which is similar to the sproutings of capillary angiogenesis. In the high-flow induced arterial remodeling, however, almost all the protrusions were capped by SMCs, finally forming EC-SMC couplings. When SMCs proliferate, IEL, which is pinned by the coupling between ECs and SMCs, would be stressed finally to be tore forming IEL-gaps. Therefore we consider that IEL-gaps are comparable with angiogenesis.
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