Lipid Transport Aspects of Atherogenesis

Abstract

In this review we shall examine the current understanding of events that lead to the incipient formation of the early foam cell lesion in atherogenesis and its localization. Particular emphasis will be placed on the intimal transport mechanisms that lead to the growth of extracellular lipid liposomes in the intima, since there is now substantial evidence that this growth is the triggering event in the complex sequence of processes that leads to the recruitment of blood borne monocytes into the sub-endothelial intima and their subsequent conversion to macrophages. The role of the endothelium, intimal proteoglycans and internal elastic lamina (IEL) in modulating the transport of low density lipoproteins (LDL) in the subendothelial space will be analyzed and a new hypothesis for the co-localization of liposome formation, cellular level endothelial leakage and monocyte entry described. The possible modifications of LDL in the lipsomes that facilitate the conversion of monocytes into foam cells is summarized. We also discuss the fluid dynamic aspects of intimal transport and the relationship of fluid shear stress to the localization of cellular level endothelial leakage of LDL. The effect of fluid shear on other endothelial cell functions has been recently reviewed in [1].