Abstract 1356: Endothelial Cell Toll-Like Receptor 2 Expression And Macrophage Number Are Increased At Sites Of Disturbed Blood Flow In The Mouse Aorta
Current knowledge demonstrates Toll-like receptors (TLRs) are essential in innate immunity but less is known about their role in atherosclerosis. We recently reported that TLR2-mediated cell signaling is proatherogenic when expressed by non-bone marrow derived cells, such as endothelial cells. Using in situ immunofluorescence and laser scanning confocal microscopy, we observed aortic endothelial expression of TLR2 in atherosclerosis-resistant C57B1/6 mice. Interestingly, the pattern of TLR2 expression closely followed the pattern of disturbed blood flow, with areas that experience turbulent blood flow demonstrating upregulation of TLR2. Next, bone marrow transplantation was performed in atherosclerosis-prone C57B1/6 low density lipoprotein receptor-deficient (LDLr−/−) mice to create chimeric mice with green fluorescent protein (GFP) expression in bone marrow-derived cells. Analysis of aortic segments from normolipidemic LDLr−/−, GFP chimeras confirmed enhanced in situ endothelial cell TLR2 expression in areas of disturbed blood flow and this was accompanied by macrophage infiltration. In hyperlipidemic, LDLr−/−, GFP chimeric mice, increased levels of both endothelial TLR2 expression and macrophage infiltration were observed. In both normo- and hyperlipid-emic animals, GFP+ cells also were found in the adventitial layers of the aorta, suggesting entry of macrophages into the adventitial layers of the aortic wall. These results documented the in vivo regiospecific expression of endothelial cell TLR2 and suggest that this receptor may contribute to the origin of lesion-prone areas in the aorta. Additionally, because both enhanced endothelial cell TLR2 expression and macrophage infiltration were observed in these areas of disturbed blood flow in lesion-resistant animals, these inflammatory participants may play a protective role in vascular tissue homeostasis in the absence of hyperlipidemia and disease.