Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids.
OBJECTIVE
Toll-like receptors (TLRs), a group of pathogen-associated microbial pattern recognition receptors, play an important role in innate immune signaling and are differentially regulated in chronic inflammatory diseases such as atherosclerosis. However, the involvement of TLRs in the progression of atherosclerosis is still unclear.


RESULTS
TLR2 and apolipoprotein E double knockout (Tlr2(-/-)Apoe(-/-)) mice were generated and the progressive formation of atherosclerotic plaque in the aortas was examined in mice fed a normal chow diet. We demonstrate that inactivation of TLR2 resulted in reduced progression of atherosclerosis in both male and female Apoe(-/-) mice. Likewise, TLR2 deficiency resulted in a reduction in lipid accumulation and decreased macrophage recruitment to the aortic sinus, as well as reduced monocyte chemoattractant protein-1 (MCP-1) levels. Furthermore, macrophages isolated from Tlr2(-/-)Apoe(-/-) mice demonstrated significantly reduced MCP-1 production upon stimulation with a TLR2 ligand. However, no differences in acetylated low-density lipoprotein uptake and foam cell formation were observed in macrophages isolated from Tlr2(-/-)Apoe(-/-) mice as compared to Apoe(-/-) mice.


CONCLUSIONS
TLR2 plays a critical role in the progression of atherosclerosis in Apoe(-/-) mice, which is independent of dietary lipids and macrophage lipid uptake.
Liu
Xinyan
X
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States.
Ukai
Takashi
T
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States; Department of Periodontology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
Yumoto
Hiromichi
H
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States; Department of Conservative Dentistry, The Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
Davey
Michael
M
Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, United States.
Goswami
Sulip
S
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States.
Gibson
Frank C
FC
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States.
Genco
Caroline A
CA
Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States; Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, United States; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address: caroline.genco@bmc.org.
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000503:physiopathology*; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005487:Foam Cells / Q000276:immunology*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000502:physiology*
D001057:Apolipoproteins E; D004041:Dietary Fats; D051195:Toll-Like Receptor 2