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- Title
Specific loss of Toll-like receptor 2 on bone marrow derived cells decreases atherosclerosis in LDL receptor null mice.
- Authors
Hasu, Mirela; Thabet, Mohamed; Tam, Nancy; Whitman, Stewart C.
- Abstract
Innate immunity and, notably, Toll-like receptors (TLR), have an important role in atherogenesis. We have tested the hypothesis that the selective loss of TLR-2 by cells of bone marrow (BM) origin will protect low-density receptor-deficient ( Ldlr −/−) mice from both early- and late-stage atherosclerosis. BM cells from Tlr2+/+ and Tlr2−/− littermates were used to reconstitute lethally irradiated Ldlr−/− mice. Following a recovery period, mice were placed either on a diet containing 21% saturated fat - 0.15% cholesterol for 8 weeks to study early-stage atherosclerosis, or on a diet richer in cholesterol (1.5%) for 16 weeks to study late-stage atherosclerosis. Donor cell Tlr2 genotype did not alter serum cholesterol levels or lipoprotein profiles in recipient animals. After 8 weeks on the 0.15% cholesterol diet, deficiency of TLR-2 expression on cells of BM origin reduced atherosclerosis in the aortic root and the aortic arch in both genders of mice. In contrast, the BM recipients who received the 1.5% cholesterol diet for 16 weeks showed much larger lesions in the aortic root, and TLR-2 deficiency in BM cells failed to provide protection. Thus, TLR-2 expression in BM-derived cells contributes primarily to early stage atherosclerosis.
- Subjects
BONE marrow cells; ATHEROSCLEROSIS; LOW density lipoproteins; INFLAMMATION; NATURAL immunity; GENE expression; LABORATORY mice
- Publication
Canadian Journal of Physiology & Pharmacology, 2011, Vol 89, Issue 10, p737
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y11-071