Abstract
Increased plasma levels of the apoB-100-containing lipoprotein(a) (Lp(a)) are associated with an increased risk for atherosclerosis and myocardial infarction, but the mechanisms by which lipoprotein(a) may accelerate these processes remain obscure. In this study we have investigated the impact of the association of apoprotein(a) with the low density lipoprotein (LDL)-like Lp(a) particle upon specificity of receptor recognition after lipoprotein modification by malondialdehyde or transition metal-induced oxidation. We have determined that radioiodination labels both apoprotein components of Lp(a), that malondialdehyde modification produces an anionic lipoprotein comparable to native Lp(a) in Stokes' radius, and that N,N'-disubstituted 1-amino-3-iminopropene derivatives preferentially cross-link apoprotein(a) to apoB-100 protein. Like LDL, native Lp(a) is recognized in human monocyte-macrophages by the LDL receptor. Like LDL, progressive modification of Lp(a) by malondialdehyde abolishes lipoprotein recognition by the LDL receptor and produces uptake and hydrolysis by the scavenger receptor of human monocyte-macrophages. We propose that intimal retention of Lp(a) by extracellular components of the atherosclerotic reaction places the lipoprotein in a microenvironment favoring subsequent peroxidative modification. The chronic production of lipid peroxide-modified Lp(a) together with unmitigated cellular clearance by scavenger receptors may contribute to the accumulation of lipoprotein-derived lipid in macrophage-derived foam cells of the atherosclerotic reaction.
Highlights
Increased plasma levels of the apoB-100-containing are associated, presumably through disulfide linkage, with the lipoprotein(a) (Lp(a))are associated with an increased apoB-100 protein [2,3,4]
Accumulating evidence supports the proposal lipoprotein(a) (Lp(a))’ are associated with an increased risk made by Fogelman e t al. [18] in 1980 that modification of for cardiovascular disease [1].Lp(a) resembles low density native LDL by malondialdehyde andother lipid peroxides lipoprotein (LDL), the major carrier of plasma cholesterol, released in situ maybe a prerequisite to accumulation of and contains 1 mol of apoB-100 proteinper particle; it is lipoprotein-derived cholesterol by cells of the atherosclerotic distinguished from LDL by 1 or 2 mol of apoprotein(a) that reaction
We have previously demonstrated that malondialdehyde efficiently converts LDL to a form that produces intra
Summary
The physicochemical and biochemical characterizations of Lp(a) preparations in this report have previously been described in detail [4]. The apoB-100 protein of Lp(a-) accounted for 62%of the radiolabel. This approach indicated that radioiodination of Lp(a) produced labeling of both the apoB-100 protein and apoprotein(a)components. Several reports have described the lability of Lp(a) at pH values
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