Abstract
Atherosclerosis is a progressive disorder of medium-to large-size arteries characterized by hardening and narrowing of the vessels due to formation and calcification of atheromatous plaques on the inside of the vessel walls. It is established that this disorder develops near vessel bifurcations and curvatures (where separation and reversal of blood flow occur) as a result of oxidative damage to vascular endothelium caused by oxidized low-density lipoproteins (oxLDL). Such endothelial dysfunction leads to increased adhesion of monocytes to endothelial cells and accumulation of monocytes/macrophages in the intimal layer of the arterial wall. In this talk, we present three-dimensional computational models of monocyte-endothelium interactions that take into account 1) monocyte viscoelasticity, 2) complex flow conditions existing at atherosclerosis-prone sites, and 3) chemokine-stimulated and multiple-receptor-mediated cell adhesion kinetics. We also discuss our in vitro experiments on oxLDL-induced adhesion of monocytic cell line THP-1 to HUVEC in a micro-fluidic flow chamber. Through comparison of in vitro and computational studies, we show that firm adhesion of monocytes to endothelial cells is very sensitive to monocyte rheological properties and flow conditions to which endothelial cells and monocytes are exposed.