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

• Published in: Canadian journal of physiology and pharmacology 2011-10, Vol.89 (10), p.737-742
• Main Authors: HASU, Mirela, THABET, Mohamed, TAM, Nancy, WHITMAN, Stewart C
• Format: Article
• Language: English
• Subjects: Animals; Aorta - pathology; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - etiology; Atherosclerosis - genetics; Atherosclerosis - pathology; Atherosclerosis - physiopathology; Atherosclerosis - prevention & control; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation - physiology; Cells; Cellular signal transduction; Cholesterol - blood; Cholesterol, Dietary - adverse effects; Diet, Atherogenic - adverse effects; Female; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genotype & phenotype; Lipoproteins - blood; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pathogenic microorganisms; Physiological aspects; Receptors, LDL - genetics; Receptors, LDL - radiation effects; Rodents; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - physiology; Toll-like receptors; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y11-071

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.