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

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 effecti...