Specific loss of Toll-like receptor 2 on bone marrow derived cells decreases atherosclerosis in LDL receptor null mice

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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.

Keywords: Toll-like receptor-2; atherosclerosis; athérosclérose; bone marrow transplant; greffe de moelle osseuse; immunité innée; inflammation; innate immunity; lipoproteins; lipoprotéines; low density lipoprotein receptor; récepteur de lipoprotéines de faible densité; récepteur-2 de type Toll

Document Type: Research Article

DOI: http://dx.doi.org/10.1139/y11-071

Affiliations: Vascular Biology Group, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada.

Publication date: October 9, 2011

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