A model for the initiation and growth of extracellular lipid liposomes in arterial intima.

Abstract

There is considerable evidence that lipoprotein cholesterol, after crossing the arterial endothelium and entering the intima from the vascular lumen, lodges in extracellular lipid packets (labeled "liposomes") bound to the extracellular matrix. These liposomes appear to form by occasional attachment of a low-density lipoprotein (LDL) to the intimal matrix and to grow in place mainly by appending available free LDL. The liposome size distributions observed in chronically hypercholesteremic (WHHL) and in short-term cholesterol-fed rabbits are quite different. We propose a hierarchy of simple nucleation-polymerization models to describe liposome formation and growth. Even the simplest of these (with only one adjustable parameter) agrees extremely well with the WHHL data. In contrast, the cholesterol-fed rabbit data seem to result from the short-term nonuniform intimal history of LDL supply, which is a consequence of the focal nature of the transendothelial LDL flow through isolated transient leakyjunctions. The same models used for the WHHL data, together with this intimal nonuniformity, superimposed on a slow uniform transendothelial seepage also account very well for this cholesterol-fed rabbit data.