Study on localization of atherogenesis

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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