| Project/Area Number |
15300150
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KARINO Takeshi Hokkaido Univ., Research Institute for Electronic Science, Prof., 電子科学研究所, 教授 (30241384)
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| Co-Investigator(Kenkyū-buntansha) |
NIWA Kouichi Tokyo Univ.of Agriculture, Fac.of Bioindustry, Assoc.Prof., 生物産業学部, 助教授 (20301012)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | Atherosclerosis / Anastomotic intimal hyperplasia / Artificial vascular graft / Blood flow / Lipoprotein / Monocyte / Endothelial cell / Smooth muscle cell / 血管 / LDL / 水透過速度 / 血管病 |
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| Research Abstract |
The aim of this research was to elucidate the mechanisms of localization of vascular diseases such as atherosclerosis, anastomotic intimal hyperplasia, and formation of cerebral aneurysms that accompany thickening or thinning of the vessel wall. For this purpose, we prepared a realistic model of an arterial wall (model artery) by co-culturing bovine aortic smooth muscle cells and endothelial cells on a porous membrane or a graft, and studied the effects of a shear flow and water filtration on surface concentration of LDL, uptake of LDL by the cells, and proliferation of the cells of the model artery. We also studied the effect of water filtration at the vessel wall on the development of intimal hyperplasia by implanting three kinds of artificial grafts into the femoral artery of the dog. It was found that (i)due the presence of water filtration flow at the vessel wall, concentration polarization of LDL occurred at the luminal surface, resulting in the accumulation and enhanced uptake of LDL by the cells of the model artery under low flow hence low shear conditions, (ii)the degree of intimal hyperplasia was greatly affected by the presence of water filtration and it was the lowest in the graft that showed the lowest filtration velocity as measured prior to its implantation, (iii) proliferation of the cells of the model artery and adhesion onto and invasion of human blood monocytes (THP-1 cells) into the wall of the model artery were greatly affected by the presence of a recirculation flow, and they were the highest around the stagnation and reattachment points of the separated flow where the flow velocity and wall shear stress were the lowest. These results strongly support our idea that flow-dependent concentration polarization of LDL is playing a key role in the pathogenesis and localization of vascular diseases mentioned above.
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