Apolipoprotein E is the determinant that mediates the receptor uptake of beta-very low density lipoproteins by mouse macrophages

Arteriosclerosis. Jan-Feb 1986;6(1):114-22. doi: 10.1161/01.atv.6.1.114.

Abstract

Beta very low density lipoproteins (beta-VLDL) from cholesterol-fed animals from patients with Type III hyperlipoproteinemia are internalized by a receptor-mediated process in mouse macrophages. Once internalized, the cholesteryl esters of beta-VLDL are hydrolyzed in lysosomes, and the released cholesterol is re-esterified, resulting in a massive accumulation of cholesteryl esters. In the present study, competitive binding experiments demonstrated that canine apo E HDLc (lipoproteins that contain almost exclusively apolipoprotein E) inhibited the receptor-mediated uptake of 125I-beta-VLDL. The incorporation of human apo E into beta-VLDL was also shown to modulate binding. Reductively methylated beta-VLDL (methyl beta-VLDL) were not taken up by macrophages and did not stimulate cholesteryl ester synthesis. When unmodified human apo E-3 was incorporated into the lipoprotein in place of the canine methyl apo E, these hybrid beta-VLDL (methyl beta-VLDL [E-3]) were internalized and degraded and were as effective as native beta-VLDL in stimulating cholesteryl ester synthesis in macrophages. In the reverse experiment, the incorporation of methyl apo E-3 into native canine beta-VLDL (beta-VLDL [methyl E-3]) reduced the binding activity of the beta-VLDL and abolished their ability to stimulate cellular cholesteryl ester synthesis. Canine beta-VLDL into which apo E-2(Arg158----Cys) had been incorporated had less ability to stimulate cholesteryl ester synthesis (20%) than did native beta-VLDL, but they were more active than beta-VLDL [methyl E-2] or beta-VLDL [methyl E-3], which had virtually no activity. These results demonstrate that apo E is the determinant mediating the receptor binding and uptake of beta-VLDL by mouse macrophages.

MeSH terms

  • Animals
  • Apolipoproteins E / metabolism*
  • Cells, Cultured
  • Cholesterol Esters / metabolism
  • Dogs
  • Fibroblasts / metabolism
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, VLDL / metabolism*
  • Macrophages / metabolism*
  • Mice
  • Peritoneal Cavity / cytology
  • Receptors, LDL / metabolism*
  • Structure-Activity Relationship

Substances

  • Apolipoproteins E
  • Cholesterol Esters
  • Lipoproteins, HDL
  • Lipoproteins, VLDL
  • Receptors, LDL
  • VLDL receptor