The Roles of Toll-Like Receptors in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the arteries that is characterised by the activation of endothelial cells, the recruitment of monocytes into the vessel wall and the differentiation of recruited macrophages into cholesterol-laden foam cells. Recent evidence from a variety of experimental approaches has indicated that Toll-like receptors (TLRs), which serve to initiate inflammatory signalling in response to the detection of molecules associated with microbial infection or tissue damage, play key roles in the development of atherosclerosis. This review summarises the recent evidence implicating TLR-dependent signalling in the activation of vascular cells during atherogenesis, and the mechanisms by which TLR-signalling may promote the dysregulation of macrophage cholesterol metabolism that is a prerequisite for the formation of foam cells and lesion progressionin vivo. Particular attention is paid to the recent studies aimed at identifying potential ligands of the TLRs that may be relevant to atherogenesis, and the diverse mechanisms by which vascular tissues may become exposed to ligands of the TLRs.