Lipoprotein Labeling and Analysis Techniques

Abstract

In human plasma Low Density Lipoprotein (LDL) is the major transport protein for endogenous cholesterol being transferred between body tissues. It is a spheric macromolecule (d 2160 nm, MW 2600 kD) with a lipid core consisting mainly of cholesterol esters (42 % w/w of LDL), phospholipids (22 %), free cholesterol (8 %) and triglycerides (6 %). The particle surface is formed by a protein helix (22 %), in case of LDL apoprotein B-100 (MW 500 kD) which is recognized by specific receptors located on the surface of liver cells and other tissue cells whereas vascular cells contain only very few LDL receptors. This leads to receptor binding of LDL followed by cellular uptake and lysosomal degradation of about 2/3 of LDL particles thereby maintaining cholesterol homeostasis¹. Reduced numbers or reduced activity of LDL receptors cause elevated plasma cholesterol levels that are associated with progression of atherosclerosis. Localized endothelial damage promotes increased uptake (not yet proven to be LDL-receptor-mediated) and degradation of LDL by vascular smooth-muscle cells and macrophage foam cells of the intima. These are the earliest detectable events that can develop into an atherosclerotic plaque^{2, 3}. Thus high interest is evident in radiolabeled LDL as tracer and receptor ligand to study these processes.