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

B. J. McKeone, J. R. Patsch, H. J. Pownall

Research output: Contribution to journalArticle

73 Scopus citations

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 37°C, 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 of apo 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 cells.

Original languageEnglish (US)
Pages (from-to)1926-1933
Number of pages8
JournalJournal of Clinical Investigation
Volume91
Issue number5
DOIs
StatePublished - 1993

Keywords

  • Apo B/E receptor
  • Apolipoprotein B
  • Atherosclerosis
  • Hypertriglyceridemia
  • Lipoproteins

ASJC Scopus subject areas

  • Medicine(all)

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