Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice.
Scavenger receptors, which include various classes, play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins, resulting in the massive accumulation of cholesteryl esters. Because macrophage-derived foam cells are considered to be an important feature in early atherogenesis, we investigated the role of scavenger receptor class A (SR-A) overexpression, especially on macrophages in lipoprotein metabolism and atherosclerosis. Bone marrow from human SR-A (MSR1)-overexpressing mice was transplanted into irradiated low density lipoprotein receptor knockout [LDLR(-/-)] mice. The transplantation resulted in an increase in total serum cholesterol (approximately 15 to 25%), especially in the VLDL fraction, when compared with LDLR(-/-) mice that were transplanted with bone marrow of wild-type littermates. Quantification of atherosclerotic lesions in the mice that were fed a "Western-type" diet for 3 months revealed that there were no differences in mean lesion area between LDLR(-/-) mice transplanted with MSR1 overexpressing and wild-type littermate bone marrow, despite increased scavenger receptor activity in vitro. The presence or absence of the LDLR in the transplanted bone marrow did not influence these results.In conclusion, introduction of MSR1-overexpressing bone marrow in LDLR(-/-) mice via bone marrow transplantation resulted in a slight increase in lipoprotein levels, but had no effect on the atherosclerotic lesion area, despite increased scavenger receptor activity in vitro.
Herijgers
N
N
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, 2333 AL Leiden, The Netherlands.
de Winther
M P
MP
Van Eck
M
M
Havekes
L M
LM
Hofker
M H
MH
Hoogerbrugge
P M
PM
Van Berkel
T J
TJ
D000107:Acetylation; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A
D015815:Cell Adhesion Molecules; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; C032629:acetyl-LDL