Role of leukocyte-specific LDL receptors on plasma lipoprotein cholesterol and atherosclerosis in mice.
Bone marrow-derived macrophages and lymphocytes express LDL receptors (LDL-R), which allow these cells to take up cholesterol-rich lipoproteins. Although these cells are ubiquitously distributed in the body, it is not known whether they influence plasma cholesterol. Macrophages and T lymphocytes also are found in atherosclerotic lesions, but it is not known whether their LDL-R expression plays a role in atherosclerosis. To address these questions, we subjected LDL-R -/-mice to total body irradiation to eliminate their endogenous bone marrow-derived cells and repopulated them with either LDL-R-expressing wild-type bone marrow (treated mice) or LDL-R -/- bone marrow (control mice). Thus, the only difference between the two groups of mice was the ability of the bone marrow-derived cells to express the LDL-R in the treated mice. Plasma cholesterol levels were similar in the two groups of mice at 8 and 16 weeks after transplantation. Chromatographic separation of the lipoproteins revealed similar lipoprotein cholesterol distributions. Although the extent of lesion area in the aortic valves of the high-fat-diet-fed mice was more severe than that in the chow-fed mice, lesions appeared similar between control and treated mice given either chow or high-fat diet. Abundant LDL-R expression was detected in the lesions of treated mice, whereas the lesions of control mice showed no LDL-R expression, indicating that donor-derived leukocytes had migrated into the lesions of the recipient mice. Thus, bone marrow transplantation can be used as a tool to replace the endogenous bone marrow-derived cells in the artery wall with those of the donor origin.
Boisvert
W A
WA
Scripps Research Institute, Department of Immunology, La Jolla, CA 92037, USA.
Spangenberg
J
J
Curtiss
L K
LK
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood*; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000378:metabolism / Q000502:physiology*
D008074:Lipoproteins; D011973:Receptors, LDL; D002784:Cholesterol