Low Density Lipoprotein Receptor of Macrophages Facilitates Atherosclerotic Lesion Formation in C57Bl/6 Mice

Abstract

Abstract-Macrophage-derived foam cells play an important role in the initiation and progression of atherosclerosis. To examine the role of the macrophage low density lipoprotein receptor (LDLr) in atherosclerotic lesion formation, bone marrow from LDLr knockout [LDLr(Ϫ/Ϫ)] mice was transplanted into irradiated wild-type C57Bl/6 [LDLr(ϩ/ϩ)] mice. After 3 months on an atherogenic diet, C57Bl/6 mice, reconstituted with LDLr(Ϫ/Ϫ) bone marrow, showed a mean lesion area of 34.7ϫ10 3 Ϯ22.4x10 3 m 2 compared with 100.8ϫ10 3 Ϯ33.0ϫ10 3 m 2 (PϽ0.001) in control C57Bl/6 mice that were transplanted with LDLr(ϩ/ϩ) bone marrow. There were no significant differences in total serum cholesterol, triglyceride levels, and lipoprotein profiles between the 2 groups. Histochemical analysis of macrophage LDLr expression in the atherosclerotic lesions indicated that C57Bl/6 mice, reconstituted with LDLr(ϩ/ϩ) bone marrow, showed extensive staining of the foam cells in the atherosclerotic lesions, whereas mice reconstituted with LDLr(Ϫ/Ϫ) bone marrow showed only a few LDLr-positive foam cells. In vitro, peritoneal macrophages isolated from wild-type C57Bl/6 mice were, respectively, 4.7-and 10.7-fold more effective in cell association and degradation of atherogenic 125 I-␤-very low density lipoprotein than were LDLr(Ϫ/Ϫ) peritoneal macrophages, establishing that the LDLr on macrophages is important for the interaction of macrophages with ␤-very low density lipoprotein. It is concluded that the LDLr on macrophages can facilitate the development of atherosclerosis, possibly by mediating the uptake of atherogenic lipoproteins. (Arterioscler Thromb Vasc

Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact

“…Indeed, numerous viral receptors have been found on effector cells. For example, the rhinovirus receptors, low-density lipoprotein and very-low-density lipoprotein, are found on macrophages (45)(46)(47). The respiratory syncytial virus receptor, CX3CR1 (48,49), is found on intestinal macrophages, whereas CD81, an entry factor for hepatitis C virus, is also found on macrophages (50,51).…”

Bone Marrow Transplantation Reveals That Recipient AT1a Receptors Are Required to Initiate Angiotensin II–Induced Atherosclerosis and Aneurysms

“…All the donor mice were LDL receptor-deficient to circumvent the possibility of its presence influencing the development of atherosclerosis, even though this is unlikely in LDL receptorϪ/Ϫ recipients. [33][34][35] If bone marrow-derived stem cells are critical to AngII-induced vascular disease, then reductions in disease with transplantation of AT1aϪ/Ϫ donors into ϩ/ϩ recipients should be balanced by restoration of disease when ϩ/ϩ donors are transplanted into Ϫ/Ϫ recipients. Using this approach, our results clearly demonstrate that AT1a receptors in the recipient are required for the initiation of AngIIinduced vascular diseases, as absence of vascular pathology in AT1a receptorϪ/Ϫ recipients could not be overcome by AT1a receptor expression in bone marrow-derived stem cells.…”

Reduced cholesterol absorption upon PPARδ activation coincides with decreased intestinal expression of NPC1L1

“…Thioglycollate-elicited peritoneal macrophages of treated and untreated DBA/1 wild-type mice were harvested as described by Herijgers et al (16). Cells were washed, and RNA isolation, cDNA synthesis, and real-time PCR were performed as described.…”