Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E
| Autor: | Terence M. Doherty, Tripathi B. Rajavashisth, Kathrin S. Michelsen, Shizuo Akira, Wenxuan Zhang, Juliana Yano, Prediman K. Shah, Michelle H. Wong, Moshe Arditi |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Apolipoprotein E Apolipoprotein B Arteriosclerosis Receptors Cell Surface Inflammation Biology Proinflammatory cytokine Mice Apolipoproteins E medicine Animals Humans Receptors Immunologic Aorta Cells Cultured Chemokine CCL2 Adaptor Proteins Signal Transducing Mice Knockout Toll-like receptor Membrane Glycoproteins Multidisciplinary Innate immune system Macrophages Toll-Like Receptors Endothelial Cells Membrane Proteins Biological Sciences Lipid Metabolism Antigens Differentiation Interleukin-12 Lipids Immunity Innate Isoenzymes Mice Inbred C57BL Toll-Like Receptor 4 Phenotype Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Myeloid Differentiation Factor 88 Immunology biology.protein TLR4 Female lipids (amino acids peptides and proteins) medicine.symptom Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:10679-10684 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0403249101 |
| Popis: | Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid differentiation factor 88 (MyD88) play an essential role in the innate immune responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is associated with a significant reduction of aortic plaque areas in atherosclerosis-prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia, implying an important role for the innate immune system in atherogenesis. Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques. Endothelial-leukocyte adhesion in response to minimally modified low-density lipoprotein was reduced in aortic endothelial cells derived from MyD88-deficient mice. Taken together, our results suggest an important role for TLR4 and MyD88 signaling in atherosclerosis in a hypercholesterolemic mouse model, providing a pathophysiologic link between innate immunity, inflammation, and atherogenesis. |
| Databáze: | OpenAIRE |
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