Analysis of Interaction between Local Blood Flow and Vascular Endothelial Cell by High Speed Three Demensional Dynamic Image Analyzer

虽然从受体分子生物学、脂质代谢和病理分析等方面对动脉粥样硬化的发生和发展进行了大量的研究，但对动脉粥样硬化的定位机制的研究却很少。由于动脉粥样硬化的特征之一是其局限于动脉的弯曲或分叉处，因此近年来许多研究者将局部血流结构作为动脉粥样硬化的始动因素而受到关注。本研究从血管内皮细胞的功能、内皮细胞与单核细胞的相互作用等方面，分析了导致动脉粥样硬化定位的初始过程。内皮型一氧化氮合酶（eNOS）荧光标记抗体染色，一氧化氮（NO）的产生用荧光物质DAF 2显色。肾动脉与主动脉分叉处内皮型一氧化氮合酶表达减少，一氧化氮生成不均匀，易发生动脉粥样硬化 ...更多信息 发生。另一方面，在动脉粥样硬化易发区细胞粘附分子的表达增加。NO可阻止血小板粘附，抑制血管平滑肌的生长，从而抑制动脉粥样硬化的发生。利用细胞-基质阻抗传感系统（ECIS）分析了单核细胞粘附对内皮细胞运动的影响。白细胞介素刺激的内皮细胞与单核细胞粘附后1小时内，阻抗显著降低。这种阻抗的降低主要是由于电池到基板空间的增加，而不是由于电池到电池空间的增加。我们认为局部血流条件可能通过eNOS表达减少导致NO生成减少和粘附分子表达增加导致单核细胞粘附增加而启动动脉粥样硬化。单核细胞通过信号转导系统使内皮细胞与基质的粘附松动。少

Although there are many studies by using molecular biology of receptor, lipid metabolism and pathological analysis to analyze the initiation and evolution of atherosclerosis, there are only few studies about the mechanism of localization of atherosclerosis. As one of the characteristic features of atherosclerosis is its localization to curvature or bifurcation of artery, recently many researchers pay attention to the local blood flow structure as an initiator of atherosclerosis. In this study we focused on the function of vascular endothelial cell and interaction of endothelial cell and monocyte, and analyzed the initial process, which leads the localization of atherosclerosis. The endothelial nitric oxide synthase (eNOS) was stained with fluorescent labeled antibody, and nitric oxide (NO) production was visualized fluorescence material DAF2. The eNOS expression and NO production was reduced and heterogeneous at the bifurcation of renal artery from aorta, where atherosclerosis is prone … More to occur. On the other hand, the expression of cell adhesion molecule was increased at the atherosclerosis-prone area. NO prevents adhesion of platelets and suppress the growth of vascular smooth muscle, and thus inhibits the initiation of atherosclerosis. We analyzed the effect of adhesion of monocyte to endothelial cell motion by the electric cell-substrate impedance sensing system (ECIS). Within one hour after monocyte adhesion to interleukin stimulated endothelial cell, the impedance decreased substantially. This decrease of impedance is mainly due to the increase off cell to substrate space, not to the increase of cell to cell space. We conclude that the local blood flow condition may initiate atherosclerosis via the decrease of NO production due to the decreased expression of eNOS and the increase of monocyte adhesion due to the increase of the expression of adhesion molecule. The monocyte loosens the attachment of endothelial cell to the substrate via the signal transduction system. Less