(59b) Transport in Vessel Walls: Why Some Vessels Get Atherosclerosis and Others Don't

Atherosclerosis is the leading cause of death, both above and below age 65, in the United States and all Western countries. It afflicts mainly large, relatively thick-walled arteries and valves, leaving smaller arteries and veins disease-free under normal conditions. Atherosclerosis appears to begin with the transport of low-density lipoproteins (LDL) cholesterol from the blood across the interfacial monolayer of endothelial cells and its accumulation inside the artery wall. This is believed to trigger the cascade of processes that lead to lesion formation. Our earlier studies have shown that LDL transport into the aortic wall is a convection/diffusion process and have modeled the kinetics of its accumulation reactions. It is natural to hypothesize that vessel-vessel differences in these transport and accumulation processes dictate why some vessels get atherosclerosis and others do not. Clearly, only a detailed understanding of how these processes differ in vessels of different atherosclerotic susceptibilities can test this hypothesis. In this talk we compare the aorta, a large, atherosclerosis-prone artery, with the smaller, rarely atherosclerotic pulmonary artery and the inferior vena cava, a vein that is normally immune to disease. We review the basic features of the transport and accumulation in the large arteries and go through a number of new sets of experiments ? both structure studies as well as water and tracer transport experiments - from our lab that shed light on the differences in transport processes in these vessels. We address the role of convection transport into the walls of each vessel, in view of each vessel's very different transmural pressure that drives such transport and see what inferences one can draw as to the differences in susceptibility. Finally, time permitting, we use these experimental measurements to construct transport theories that explains the similarities and differences between these vessels. Combination these theories with the lipid accumulation kinetics mentioned above seems to shed some light on why certain chronic conditions, such as pulmonary hypertension, can shift the balance in certain vessels from resistant to susceptible.