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Interaction of very-low-density lipoprotein isolated from type I (insulin-dependent) diabetic subjects with human monocyte-derived macrophages

Authors
Journal
Metabolism
0026-0495
Publisher
Elsevier
Publication Date
Volume
38
Issue
11
Identifiers
DOI: 10.1016/0026-0495(89)90048-6
Disciplines
  • Biology
  • Chemistry
  • Medicine

Abstract

Abstract Very-low-density lipoproteins (VLDL) (density < 1.006 g/mL) were isolated from type I (insulin-dependent) diabetic patients in good to fair glycemic control and from age-, sex-, and race-matched, nondiabetic, control subjects. VLDL were incubated with human, monocyte-derived macrophages obtained from nondiabetic donors, and the rates of cellular cholesteryl ester synthesis and cholesterol accumulation were determined. VLDL isolated from diabetic patients stimulated significantly more cholesteryl ester synthesis than did VLDL isolated from control subjects (4.04 ± 1.01 v 1.99 ± 0.39 nmol 14C-cholesteryl oleate synthetized/mg cell protein/20 h; mean ± SEM, P < .05). The stimulation of cholesteryl ester synthesis in macrophages incubated with VLDL isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation ( P < .05). The increases in cholesteryl ester synthesis and accumulation in macrophages were mediated by a significant increase in the receptor mediated, high affinity degradation (2.55 ± 0.23 v 2.12 ± 0.20 μg degraded/mg cell protein/20 h) and accumulation (283 ± 35 v 242 ± 33 ng/mg cell protein/20 h) of 125I-VLDL isolated from diabetic patients compared with VLDL from control subjects. To determine if changes in VLDL apoprotein composition were responsible for the observed changes in cellular rates of cholesteryl ester synthesis and accumulation, we also examined the apoprotein composition of the VLDL from both groups. There were no significant differences between the apoproteins B, E, and C content of VLDL from both groups. We also determined the chemical composition of VLDL isolated from both groups of subjects. The free cholesterol content of VLDL isolated from diabetic patients increased significantly and, thus, also contributed to the increased rates of cellular cholesteryl ester synthesis and accumulation. In conclusion, we have shown that VLDL isolated from Type I diabetic patients interact abnormally with human macrophages, and this altered interaction may contribute to the increased prevalence of atherosclerosis in diabetes.

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