title: Specific loss of toll-like receptor 2 on bone marrow derived cells decreases atherosclerosis in LDL receptor null mice.
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.
authors: Vascular Biology Group, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada.
authors: Mirela
authors: M
authors: Hasu
authors: Mohamed
authors: M
authors: Thabet
authors: Nancy
authors: N
authors: Tam
authors: Stewart C
authors: SC
authors: Whitman
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004036:Diet, Atherogenic / Q000009:adverse effects; D005260:Female; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000528:radiation effects; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*
chemical_list: D002791:Cholesterol, Dietary; D008074:Lipoproteins; D011973:Receptors, LDL; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D002784:Cholesterol