Specific loss of Toll-like receptor 2 on bone marrow derived cells decreases atherosclerosis in LDL receptor null mice*The senior author, Stewart C. Whitman, passed away on 19 February 2010. The manuscript has been communicated by Ross W. Milne (e-mail: rmilne@ottawaheart.ca) and Yves L. Marcel (e-mail: ylmarcel@ottawaheart.ca), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada
| Autor: | Mohamed Thabet, Stewart C. Whitman, Mirela Hasu, Nancy Tam |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
medicine.medical_specialty Physiology Cholesterol Saturated fat Inflammation General Medicine Biology chemistry.chemical_compound TLR2 Endocrinology medicine.anatomical_structure chemistry Physiology (medical) Internal medicine LDL receptor medicine Bone marrow medicine.symptom Receptor Lipoprotein |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 89:737-742 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y11-071 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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