Toll-like receptor 4 in atherosclerosis

Abstract

Toll-like receptor 4 (TLR4) is key regulators of both innate and adaptive immune responses. TLR4 recognizes pathogen-associated molecular patterns (PAMPs) and activates the inflammatory cells. The function of TLR4 in atherosclerosis has been investigated in mouse knockout studies and epidemiological studies of human TLR4 polymorphisms. These studies have shown that TLR4 function affects the initiation and progression of atherosclerosis. This article reviews the biological functions and clinical implications of TLR4 in atherosclerosis.

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TLR4 signaling pathway and its relation with atherosclerosis. Both endogenous and exogenous ligands can activate TLR4 on cells, such as endothelial cells, vascular smooth muscle cells, adventitial fibroblasts, dendritic cells and macrophages. Activated TLR4 lead to activation of the transcription factor nuclear factor κ B-(NF-κB) or IRF3-responsive genes. Activated transcription factors mediate secretion of pro-inflammatory cytokines and chemokines and also induce expression of adhesion molecules. Ultimately, these processes might initiate or promote atherosclerotic lesions.