[Role of hemodynamic factors in atherogenesis]

Since atherosclerotic lesions are apt to occur at specified regions in the blood vessels, hemodynamic factors, such as shear stress generated by blood flow, have been considered to play a role in atherogenesis. Atheroma, which is characterized by the localized accumulation of lipid and the proliferation of smooth muscle cells in the intima, appears at branching or curving sites of blood vessels, where both geometrical shape and blood flow change suddenly. In such sites, both stagnant and turbulent blood flow can occur and the direction and intensity of shear stress, acting on the vascular wall, changes transiently. Recent studies using cultured endothelial cells (EC) and flow-loading apparati have demonstrated that shear stress modulates various EC functions. Shear stress alters EC macromolecular permeability and affects the production of growth factors, by the EC, which stimulate smooth muscle cell proliferation. Shear stress also exerts an influence on EC turnover, which might be involved in the transport of low-density lipoproteins via leaky junctions. Furthermore, shear stress modulates the interaction between leukocytes and EC by changing the expression or functions of adhesion molecules. It is very likely that changes in EC functions induced by shear stress are involved in atherogenesis, but direct evidence demonstrating the role of shear stress in the initiation of atherosclerotic disease processes is still lacking. Further studies are needed to clarify the role of hemodynamic factors in atherogenesis.