Emerging role of Toll-like receptors in atherosclerosis

Abstract

Atherosclerosis is inflammation of the vessel wall of the arterial tree. This inflammation arises at specific areas that experience disturbed blood flow such as bifurcations and the lesser curvature of the aortic arch. Although all endothelial cells are exposed to comparable levels of circulating plasma cholesterol, only endothelial cells overlaying lesions display an inflamed phenotype. This occurs even in the absence of any additional exacerbating disease factors because blood flow controls the expression of Toll-like receptors (TLR), which are initiators of cellular activation and inflammation. TLR2-and 4-expression exert an overall proatherogenic effect in hyperlipidemic mice. TLR activation of the endothelium promotes lipid accumulation and leukocyte accumulation within lesions.-Curtiss, L. K., and P. S. Tobias. Emerging role of Toll-like receptors in atherosclerosis. J. Lipid Res. 2009. 50: S340-S345.

Lipopolysaccharide and Sphingosine-1-Phosphate Cooperate To Induce Inflammatory Molecules and Leukocyte Adhesion in Endothelial Cells

“…Genetic and experimental evidences link TLR4 (the first receptor identified in humans and a sensor of LPS, an outer component of Gram-negative bacteria) to atherogenesis (14). In endothelial cells, TLR activation has been reported to promote lipid uptake and adhesion of leukocytes in atherosclerotic lesions (14).…”

“…Given the role of TLR activation in promoting leukocyte accumulation within atherosclerotic lesions (14), and in light of previous studies demonstrating the role of S1P in the induction of adhesion molecules (17,18), we sought to investigate the potential interplay of TLR and S1P receptors in the adhesion and inflammatory pathways in human endothelial cells from venous and arterial origin.…”

“…TLRs are sensors of microbial components that play an important role in innate immunity (12) and the pathogenesis of several inflammatory diseases such as systemic lupus erythematosus, sepsis, and atherosclerosis (13,14). Genetic and experimental evidences link TLR4 (the first receptor identified in humans and a sensor of LPS, an outer component of Gram-negative bacteria) to atherogenesis (14).…”

Relationship between serine dipeptide lipids of commensal Bacteroidetes and atherosclerosis

“…Accumulation of Lipid 654 in human tissues indicated that an exogenous TLR2 ligand was present and originated from organisms either of the oral cavity or the intestinal tract. TLR2 is known to be an important immune receptor in the development of atherosclerosis [14–16], and it is upregulated in endothelial cells subjected to turbulent fluid flow [17,18]. …”

Toll in the vessel wall—for better or worse?

“…Innate as well as adaptive immunity contributes to inflammation in atherosclerosis, and a spectrum of TLRs are expressed in the human atherosclerotic plaque (4). Experiments in gene-targeted models show that certain TLRs impact on atherosclerosis in hypercholesterolemic mice (5,6). Specifically, TLR2 and TLR4 ligations promote disease development, whereas ablation of these receptors reduces lesion size (7,8).…”