Cholesterol accumulation in J774 macrophages induced by triglyceride-rich lipoproteins. Comparison of very low density lipoprotein from subjects with type III, IV, and V hyperlipoproteinemias.

摘要: The capacity of human triglyceride-rich lipoproteins to induce cholesterol accumulation in the murine J774 macrophage cell line was investigated with large very low density lipoprotein (VLDL, Sf 60-400) obtained from subjects type III, IV, and V hyperlipoproteinemias. After incubation for 24 hours, VLDLs IV were similar their ability raise cellular deposition threefold fourfold triglyceride 16-fold. increase entirely due dramatic ester, less than 1 greater 50 micrograms/mg protein. Total fivefold observed VLDL or (LDL) normal subjects. Cholesterol esterification (acyl coenzyme A: acyltransferase [ACAT] activity) paralleled rate these cells. Treating macrophages ACAT inhibitor 58035, which is known downregulate LDL receptor cells, diminished by 40% 23% LDL. Since hypertriglyceridemic carries excess apoprotein (apo) E molecules, we role abnormal apo E. An anti-apo monoclonal antibody, block binding receptor, blocked VLDL-induced ester approximately 70%. In contrast subjects, III (homozygous E2) when incubated (which do not secrete E) caused only a modest 1.5-2-fold cholesterol. Pre-beta- beta-migrating subfractions equally ineffective causing accumulation. By contrast, beta-VLDL cholesterol-fed rabbits sevenfold eightfold content. These results indicate that can cause substantial enhanced lower presence antibodies demonstrates importance functional this process.