Plasma triglycerides determine low density lipoprotein composition, physical properties, and cell-specific binding in cultured cells.

Abstract

The relationship between the plasma triglycerides and the LDL triglycerides of 30 normal and 48 hypertriglyceridemic subjects has been quantified; the data fit a simple adsorption isotherm, LDL triglyceride/(LDL triglyceride + LDL cholesterol ester) = 0.65 plasma triglyceride/(464 + plasma triglyceride). In vitro transfer of triglyceride from concentrated VLDL to VLDL-depleted plasma produced triglyceride-rich LDL that had similar properties. LDL uptake by HepG2 cells increased with LDL triglyceride content whereas the reverse was found with skin fibroblasts. At 370C, the cores of both normal and hypertriglyceridemic LDL were isotropic liquids. Circular dichroic spectra revealed no difference in the secondary structure of normal and triglyceride-rich LDL. The affinity of monoclonal antibody MB47, which binds to the receptor ligand of apo B-100 was independent of LDL triglyceride content. MB3, which binds near residue 1022 ofapo B-100, showed a triglyceride-dependent decrease in affinity for LDL from hypertriglyceridemic subjects and from in vitro incubations. LDL with an elevated triglyceride content formed in vitro had reduced proteolytic cleavage of apo B-100 by Staphylococcus aureus V8 protease. From these data, we infer that (a) LDL triglyceride is a predictable function of plasma triglyceride, (b) triglyceride induces subtle changes in apo B-100 structure at a site that is remote from the putative receptor binding ligand, and (c) the triglyceride-dependent receptor-binding determinants of apo B-100 are recognized differently by fibroblasts and HepG2

Molecular Mechanism for Changes in Proteoglycan Binding on Compositional Changes of the Core and the Surface of Low-Density Lipoprotein–Containing Human Apolipoprotein B100

“…27 However, our results are not consistent with the finding that in the absence of changes in the size of the particle, the relative content of neutral lipid in the core of LDL does not significantly affect apoB conformation or its affinity for the LDL receptor. 28 The reasons for these differences are unclear but could reflect differences in experimental design, because the secondary structure of apoB in LDL strongly depends on the physical state of the lipoprotein core.…”

Model of human low-density lipoprotein and bound receptor based on CryoEM

“…3), the small, dense LDL is triglyceride-enriched and has an isotropic liquid core with no apparent striations according to cryoEM (18). Furthermore, the apo B-100 of triglyceride-rich LDL also shows impaired binding to fibroblast LDL receptors, suggesting an altered conformation (28,29). Thus, there is compelling evidence that the structure of the LDL core stabilizes the conformation of apo B-100 that interacts with its receptor and with the vascular endothelium.…”

Apolipoprotein B is conformationally flexible but anchored at a triolein/water interface: A possible model for lipoprotein surfaces

“…For example, apoB on plasma VLDL has a low affinity for the LDL receptor compared with LDL. LDL expresses different affinities for antibodies depending on the size and composition of the particle, and small, dense LDL has increased susceptibility to proteases and decreased affinity for the LDL receptor (19)(20)(21). The ability for active oxygen to oxidize LDL into potentially atherogenic particles is greater with small LDL compared with large LDL (22,23).…”