The Effects of Augmented Hemodynamic Forces on the Progression and Topography of Atherosclerotic Plaques

In order to clarify mechanisms determining different degrees of vulnerability of atherogenesis between the apical and the proximal lateral walls at branchings, both regions of the inferior mesenteric artery in human autopsy cases were investigated electron microscopically. The lateral wall and the apex have been accepted by many researchers as the most preferential and the most resistant sites, respectively, for the disease. In regard to blood flow, the apex is exposed to laminar high shear stress, but the outer lateral wall to turbulent low shear stress. In newborns, intimal thickness in the apex was greater than that in the lateral wall, due mainly to the proliferation of SMC. After the 3rd decade, collagen fibers drastically increased in the apical intima, and SMC embedded between the collagen fibers, modulating their phenotypes from synthetic to contractile. In the lateral intima, SMC remained as the synthetic type. Synthetic SMC are considered capable of proliferation in the arterial wall. The lateral intima was generally abundant in proteoglycans and lacked collagen (including subendothelial basement membranes) as well as elastic fibers, particularly in the upper part of the intima. Such a structural difference may cause favorable conditions for atherosclerosis. Results of in vitro studies revealed that collagen gel suppressed proliferation of SMC and changed their phenotype from synthetic to contractile. Therefore, laminar high shear stress gives the arterial wall resistancy to atherogenesis through this phenotypic change. Rabbits showed preferential regions in certain areas of the flow divider for lipid deposition which were different from those of human beings. These regions were covered by ellipsoidal endothelial cells, which should be exposed to relatively low mean shear stress. Ellipsoidal endothelial cells had already been observed in intact rabbits. Therefore, we can conclude that atherogenic processes could be initiated by relatively low mean shear stress in either humans or rabbits.