Study on localization of atherogenesis

流体切应力诱导血管内皮细胞在体外和体内条件下的形态学变化。已知动脉粥样硬化病变倾向于局限于动脉分支和弯曲部位。这些部位可能经历局部复杂的血流，如壁面切应力的升高或降低、边界层分离、二次流等，由于内皮细胞层不断受到血流产生的切应力的作用，这些部位复杂的血流模式可能直接影响细胞的形态和功能。在本研究中，我们探讨了动脉粥样硬化形成的局限性因素，从体内研究来看，升主动脉的大分子通透性高于降主动脉。此外，升主动脉和降主动脉内皮细胞VCAM-1（单核细胞粘附分子）的表达也不同。内皮细胞对单核细胞大分子通透性的调控和粘附分子的表达是其与动脉粥样硬化形成相关的重要功能。这些结果表明，升主动脉内皮细胞反映了复杂的血流模式，内皮细胞的功能受到复杂血流的影响。本研究结果为内皮细胞可能识别血流方向并改变其形状和细胞骨架结构提供了证据。此外，F-actin丝可能与切应力的敏感机制有关。我们研制了用于测量培养内皮细胞力学特性的AFM系统和利用兔主动脉段兴奋的流动实验系统

Fluid shear stress induces morphological changes of vascular endothelial cells under in vitro and in vivo conditions. It has been known that atherosclerotic lesions tend to localize at arterial branch and curved sites. Those regions would have experienced localized complex blood flows such as elevated or reduced wall shear stress, boundary layr separation, secondary flows and so on. Since the endothelial cell layr is constantly subjected to shear stress arising from blood flow, the complex blood flow pattern at these sites may affect directly cell morphology and function. In this study, we investigated the factors of localization of atherogenesis.From the in vivo studies, the macro molecular permeability in ascending aorta was higher than that in descending thoracic aorta. Moreover, VCAM-1 (adhesion molecule to monocyte) expression on the endothelial cells in ascending aorta is different from that in descending thoracic aorta. The controlling the macro molecular permeability and the expression of adhesion molecules to monocyte are important functions of endothelial cells related to atherogenesis. These results indicate that endothelial cells in the ascending aorta reflect a complex blood flow pattern and functions of endothelial cells are affected by the complex blood flow.We studied the effects of the change of flow direction on the morphology of cultured bovine aortic endothelial cells. The results of this study provide evidences that endothelial cells might recognize the flow direction and change their shape and cytoskeletal structure. Moreover, F-actin filament might be related to the sensing mechanism of shear stress.We developed the AFM system for measuring the mechanical properties of cultured endothelial cells and the new flow experimental system using the excited aortic segment from rabbit