Role of the macrophage very-low-density lipoprotein receptor in atherosclerotic lesion development.
OBJECTIVE
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.


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 x 10(3)+/-microm(2). 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 x 10 microm. The mean atherosclerotic lesion area, measured in control transplanted VLDLr-/- mice, lacking the VLDLr in all tissues was 12+/-3 x 10(3)microm(2). 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 x 10(3)microm(2).


CONCLUSIONS
The macrophage VLDLr facilitates atherosclerotic lesion development, probably by mediating the accumulation of atherogenic lipoproteins.
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. m.eck@lacdr.leidenuniv.nl
Miranda Van
MV
Eck
Jenina
J
Oost
Jeltje R
JR
Goudriaan
Menno
M
Hoekstra
Reeni B
RB
Hildebrand
I Sophie T
IS
Bos
Ko Willems
KW
van Dijk
Theo J C
TJ
Van Berkel
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016026:Bone Marrow Transplantation; D046528:Chimerism; D004195:Disease Models, Animal; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics
D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D011973:Receptors, LDL; C036053:VLDL receptor