In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 17, No. 3 ( 1997-03), p. 498-504
Abstract:
Abstract Apolipoprotein (apo) E–deficient mice display marked accumulation in the plasma of VLDL deficient in both apoE and apoB100 but containing apoB48, apoA-I, apoCs, and apoA-IV. Since apoE-deficient mice develop severe atherosclerotic lesions with lipid-laden macrophages, we reasoned that the uptake of lipoproteins by intimal macrophages can take place in the absence of both apoE and apoB100. To get more insight into the mechanism of foam cell formation in apoE-deficient mice, we measured the interaction of VLDL from apoE-deficient mice (apoE null VLDL) with the murine macrophage cell line J774. Scatchard analysis revealed that apoE null VLDL is bound to J774 cells with a K d value comparable to that of control VLDL (8.1 versus 4.7 μg/mL) and with a B max value about half that of control VLDL (40 versus 70 ng/mg cell protein, respectively). ApoE null VLDL is also taken up and degraded by J774 macrophages via a high-affinity process less efficiently than control mouse VLDL (6-fold and 50-fold less efficiently, respectively). In line with this observation, incubation of J774 cells with 50 μg/mL apoE null VLDL for 24 hours resulted in an increase in intracellular cholesteryl ester (CE) content, although 5-fold less pronounced than after incubation with 50 μg/mL control mouse VLDL. Under the conditions applied, simultaneous addition of 5 μg/mL lipoprotein lipase (LPL) stimulated the cellular uptake and degradation of apoE null VLDL about 10-fold and resulted in a 5-fold stimulation of the intracellular CE accumulation, from 9±2 to 46±5 μg CE per milligram cell protein. In contrast to control mouse VLDL, apoE null VLDL could not compete with 125 I-labeled LDL for binding to the LDL receptor of J774 cells. Furthermore, neither LDL nor acetylated LDL could compete with 125 I-labeled apoE null VLDL for binding to these cells, whereas control mouse VLDL, VLDL from a hypertriglyceridemic patient, and apoE null VLDL itself were efficient competitors. Thus, VLDL from apoE-deficient mice is taken up by J774 macrophages through recognition by a distinct receptor, which could be the triglyceride-rich lipoprotein receptor. We conclude that in apoE-deficient mice, foam cell formation occurs via a receptor-mediated uptake of apoE null VLDL, which can be stimulated by the presence of LPL.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.17.3.498
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1997
detail.hit.zdb_id:
1494427-3
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