Selective isolation of human plasma low-density lipoprotein particles containing apolipoproteins B and E by use of a monoclonal antibody to apolipoprotein B

Abstract

A monoclonal antibody to human plasma apolipoprotein B was used in a single-step immunoaffinity chromatography procedure to isolate a subpopulation of low-density lipoprotein particles from normolipidemic human plasma. The isolated particles were homogeneous in terms of size (20 nm), flotation coefficient (Sf = 9.5), and electrophoretic mobility (beta band). Their protein moiety consisted of apolipoproteins B and E in a molar ratio close to 2. The lipid moiety consisted of 47.3% cholesterol, 4.7% triglycerides, and 48.0% phospholipids. To indicate its characteristic apolipoprotein composition and hydrated density properties, this family of particles was named LP-B:EL2. In most normolipidemic subjects, LP-B:EL2 particles accounted for less than 10% of the total plasma apolipoprotein B content. The LP-B:EL2 particles bound to the membranes of the human hepatoma HepG2 cells in a specific and saturable manner indicative of receptor-mediated binding. Their binding was significantly higher than that of low-density lipoprotein particles containing only apolipoprotein B.

On the atherogenicity of triglyceride-rich lipoproteins and novel markers for the assessment of their atherogenic potentials

“…In contrast, the relative atherogenic capacities of Lp-B:C:E and Lp-B:E particles may be less pronounced than that of Lp-B particles. This might be due to high rates of the lipolytic degradation of Lp-B:C:E particles on one hand [49] and high affinity binding and uptake of Lp-B:E particles by LDL receptors on the other [50]. Under normal metabolic conditions, plasma levels of Lp-B:C:E and Lp-B:E particles are relatively low except in hypercholesterolemic and hypertriglyceridemic states [63].…”

“…Furthermore, it has been demonstrated that the three major TG-rich lipoprotein families have different affinities for lipoprotein lipase (LPL) despite almost identical TG and apoC-III contents; thus, the Lp-B:C:E particles have been found to be the most efficient substrate for LPL followed by decreasing efficiency of Lp-B:C and low efficiency of Lp-A-II:B:C:D:E particles [49]. The Lp-B:E particles bind to LDL receptors on human fibroblasts, HepG2 and HeLa cells with greater affinity than Lp-B particles [50,51]; in contrast, the binding of Lp-B:C and Lp-B:C:E particles with phenotype E2/E2 to LDL receptors of HeLa cells has been found to be negligible, suggesting that these lipoprotein families have very little effect on the regulation of HMG-CoA reductase activity [51]. All these findings provide strong evidence for the crucial role of minor apolipoproteins in modifying and determining the metabolic properties of individual apoA-and apoB-containing lipoproteins.…”

Modulation of the expression of human LDL-Apo B-100 epitopes by lipids and apolipoproteins.

“…The protein moiety is actually thought to have an important role in the formation of epitopes. In this way, Koren et al 39 have described a Cl MAb that is specific for a particular conformation of apo B expressed in lipoprotein particles containing apo B and apo E exclusively as protein components. Finally, in a recent in vivo metabolic study performed with various LDL density subpopulations from subjects with normolipidemia and familial combined hyperlipidemia, it has been suggested that the presence of non-apo B apolipoproteins could influence the metabolic behavior of different LDL subclasses.…”

Detection, Quantification, and Characterization of Potentially Atherogenic Triglyceride-Rich Remnant Lipoproteins

“…96 Sequential immunoaffinity chromatography or immunoprecipitation has revealed the existence of 3 major species of plasma lipoproteins containing both apoE and apoB 97 : LpB:C:E particles (ie, TRL containing apoC-I, C-II, C-III, and apoE); LpA-II:B:C:D:E particles (ie, TRL containing several apolipoproteins including apoA-II and apoE, characteristic of patients with Tangier disease or type V hyperlipoproteinemia 98 ); and LpB:E particles (ie, cholesteryl ester-enriched lipoproteins resembling LDL with apoE. 99 Two additional apoB-containing lipoproteins in human plasma are LpB:C particles (ie, TRL containing only C apolipoproteins) and LpB (ie, LDL containing only apoB 100 ). It remains to be determined which of these lipoprotein species best represents TRL remnants.…”