NAIKI Takeru Hokkaido univ., Res.Inst.for Electronic Scicnce, Res.Assoc., 電子科学研究所, 助手 (40241385)
WADA Shigeo Hokkaido univ., Res.Inst.for Electronic Science, Lecturer, 電子科学研究所, 講師 (70240546)
|Budget Amount *help
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1997: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
1.To elucidate the localization of vascular diseases such as atherosclerosis, intimal hyperplasia, and aneurysm formation in man, the effects of flow patterns, wall shear rate, and filtration velocity of water at a vessel wall on concentration of atherogenic low density lipoproteins (LDL) at the luminal surface of a straight portion, branching sites, curved segments, and stenotic portions of arteries were studied by means of a computer simulation of convective and diffusive transport of LDL from flowing blood to a vessel wall under the conditions of a steady flow.It was found that in all the cases, due to the concentration polarization of macromolecules at a blood/endothelium boundary, surface concentration of LDL is locally elevated in regions occupied with slow secondary and recirculation flows where wall shear rate is low and where intimal hyperplasia and atherosclerotic lesions tend to develop. On the contrary to this, in regions adjacent to the flow divider of bifurcations and rig
ht distal to an axisymmetric stenosis where wall shear rate is high and formation of saccular aneurysms and localized dilatation of vessel wall tends to occur, no accumulation of LDL occurred.
2.To substantiate the findings of the theoretical analyzes described above, the effects of wall shear rate (flow rate) on surface concentration of lipoproteins at an arterial endothelium were studied by using a cultured bovine aortic endothelial cell (BAEC) monolayr which served as a model of an arterial wall, and measuring the filtration velocity of water (cell culture medium) at the BAEC monolayr which varied secondarily as functions of lipoprotein concentration and wall shear rate. It was found that surface concentration of lipoproteins increased or decreased inverse proportionally to wall shear rate, taking the highest value at wall shear rate equals to zero. This confirmed experimentally that flow-dependent concentration or depletion of LDL at the luminal surface of an artery which has been predicted theoretically to occur certainly occurs at the surface of a cultured endothelial cell monolayr.
Based on these theoretical and experimental findings, we proposed a hypothesis that localization of vascular diseases which include atherosclerosis, cerebral aneurysms, and anastomotic intimal hyperplasia result from flow-dependent concentration polarization of LDL at a blood/endotheliun boundary. Less