The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors.

At present, it is commonly accepted that atherosclerosis is a chronic inflammatory disease characterized by disorder of the arterial wall. As one of the inflammatory cytokines of the tumor necrosis factor superfamily, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in the formation and progression of atherosclerosis. TWEAK, when binding to its initial receptor, fibroblast growth factor inducible molecule 14 (Fn14), exerts adverse biological functions in atherosclerosis, including dysfunction of endothelial cells, phenotypic change of smooth muscle cells and inflammatory responses of monocytes/macrophages. However, accumulating data supports that, besides Fn14, TWEAK also binds to cluster of differentiation (CD)163, an anti-inflammatory cytokine and a scavenger receptor exclusively expressed by monocytes and macrophages. Furthermore, it has been demonstrated that CD163 is able to internalize TWEAK and likely elicits protective effects in atherosclerosis by terminating inflammation induced by TWEAK. In the present study, the role of TWEAK in atherosclerosis was reviewed, with a predominant focus on CD163 and Fn14 receptors.