VASCULAR FLUID-MECHANICS, THE ARTERIAL-WALL, AND ATHEROSCLEROSIS

Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell's mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow-imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events. Complementary to this will be in vitro model studies of arterial fluid mechanics. In addition, one can foresee an increasing role for computer modelling in our efforts to understand the pathophysiology of the atherogenic process. This includes not only computational fluid mechanics, but also modelling the pathobiologic processes taking place within the arterial wall. A key to the atherogenic process may reside in understanding how hemodynamics influences not only intimal smooth muscle cell proliferation, but also the recruitment of the monocyte/macrophage and the formation of foam cells. Finally, it will be necessary to begin to integrate our knowledge of cellular phenomena into a description of the biologic processes within the arterial wall and then to integrate this into a picture of the disease process itself.