Role of the macrophage very-low-density lipoprotein receptor in atherosclerotic lesion development
article
Objectives: The very-low-density lipoprotein receptor (VLDLr) is highly expressed in macrophage-rich areas of atherosclerotic lesions. The exact role of the macrophage VLDLr in atherosclerotic lesion development, however, is presently unclear. Methods and results: To assess the role of the macrophage VLDLr in atherosclerotic lesion development in vivo, we used the technique of bone marrow transplantation to selectively disrupt or reconstitute the VLDLr in macrophages in VLDLr+/+ and VLDLr-/- mice, respectively. After 10 weeks high-cholesterol diet feeding, the lesion area in control transplanted wild-type mice was 17 ± 4 × 103 ± μm2. Disruption of the macrophage VLDLr by transplanting bone marrow from VLDLr-/- mice to wild-type VLDLr+/+ littermates resulted in a tendency to a slight reduction in lesion size to 12 ± 3 × 10 μm. The mean atherosclerotic lesion area, measured in control transplanted VLDLr-/- mice, lacking the VLDLr in all tissues was 12 ± 3 × 103 μm2. Interestingly, reconstitution of the macrophage VLDLr in VLDLr-deficient recipients resulted in a 2.7-fold increase (P < 0.05) in the mean atherosclerotic lesion area to 32 ± 3 × 103 μm2. Conclusions: The macrophage VLDLr facilitates atherosclerotic lesion development, probably by mediating the accumulation of atherogenic lipoproteins. © 2005 Elsevier Ireland Ltd. All rights reserved. Chemicals / CAS: Lipoproteins, VLDL; Receptors, LDL; RNA, Messenger; VLDL receptor
Topics
Biomedical ResearchAtherosclerosisBone marrow transplantationLipoproteinsMacrophageVLDL receptorvery low density lipoproteinvery low density lipoprotein receptoranimal cellanimal experimentanimal modelanimal tissueatherosclerosisbioaccumulationbone marrow transplantationcholesterol dietcontrolled studyin vivo studymacrophagemousenonhumanprotein analysisprotein expressionprotein functionprotein localizationwild typeAnimalsAorta, ThoracicAtherosclerosisBone Marrow TransplantationChimerismDisease Models, AnimalLipoproteins, VLDLMacrophagesMiceMice, Inbred C57BLPolymerase Chain ReactionReceptors, LDLRNA, Messenger
TNO Identifier
239009
ISSN
00219150
Source
Atherosclerosis, 183(2), pp. 230-237.
Pages
230-237
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