© 1997 American Heart Association, Inc.
Articles |
Role of Leukocyte-Specific LDL Receptors on Plasma Lipoprotein Cholesterol and Atherosclerosis in Mice
the Scripps Research Institute, Department of Immunology (W.A.B., J.S.) and Department of Vascular Biology (L.K.C.), La Jolla, Calif.
Correspondence to Linda K. Curtiss, PhD, The Scripps Research Institute, IMM-17, 10666 N Torrey Pines Rd, La Jolla, CA 92037. E-mail lcurtiss@scripps.edu.
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.
Key Words: mouse model • bone marrow transplantation • gene transfer • immunohistochemistry • atherogenic diet
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