Binding of Low Density Lipoproteins to Lipoprotein Lipase Is Dependent on Lipids but Not on Apolipoprotein B

Abstract

Lipoprotein lipase (LPL) efficiently mediates the binding of lipoprotein particles to lipoprotein receptors and to proteoglycans at cell surfaces and in the extracellular matrix. It has been proposed that LPL increases the retention of atherogenic lipoproteins in the vessel wall and mediates the uptake of lipoproteins in cells, thereby promoting lipid accumulation and plaque formation. We investigated the interaction between LPL and low density lipoproteins (LDLs) with special reference to the protein-protein interaction between LPL and apolipoprotein B (apoB). Chemical modification of lysines and arginines in apoB or mutation of its main proteoglycan binding site did not abolish the interaction of LDL with LPL as shown by surface plasmon resonance (SPR) and by experiments with THP-I macrophages. Recombinant LDL with either apoB100 or apoB48 bound with similar affinity. In contrast, partial delipidation of LDL markedly decreased binding to LPL. In cell culture experiments, phosphatidylcholine-containing liposomes competed efficiently with LDL for binding to LPL. Each LDL particle bound several (up to 15) LPL dimers as determined by SPR and by experiments with THP-I macrophages. A recombinant NH 2 -terminal fragment of apoB (apoB17) bound with low affinity to LPL as shown by SPR, but this interaction was completely abolished by partial delipidation of apoB17. We conclude that the LPL-apoB interaction is not significant in bridging LDL to cell surfaces and matrix components; the main interaction is between LPL and the LDL lipids.

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

“…These chemical (ratio of proteins to lipids per particle) or conformational changes of apoB proteoglycan binding site may account for the proatherogenicity of these lipoproteins. 36,38 Interestingly, LDLs from transgenic rabbits also induced a small but discernable increase of cholesteryl ester formation in macrophages even these particles are a poor ligand for LDL receptors (Figure 10). In transgenic rabbits, we detected hLPL proteins (503730 ng/ml, n ¼ 5) in preheparin plasma, accounting for about 1 3 of hLPL present in postheparin plasma.…”

pH6 antigen of Yersinia pestis interacts with plasma lipoproteins and cell membranes

“…Chloroform solutions of FC and PC (10 mg/ml) were mixed in 1:1 molar ratio and evaporated under a stream of nitrogen. After addition of 5 mM Tris-Cl, 0.15 M NaCl, 0.02% (w/v) NaN 3 (pH 7.4), sonication was for repetitive cycles as previously described (32). For some experiments, a commercial emulsion of soybean TG in egg yolk PC (Intralipid ® 10%) was used.…”

Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease

“…The differential response may relate to genotypespecific differences in LPL activity (14) and, in turn, their effects on triglyceride levels, which are known to be an important determinant of LDL composition and particle size (41). On the other hand, it is also known that LPL can bind to LDL (42), suggesting that the less common N9 allele may be associated with altered uptake of LDL during gemfibrozil therapy. Compatible with this concept, Fisher et al (43) have recently reported that the LPL N9 allele was associated with the bridging of LDL to monocytes in vitro.…”