title: Tumor necrosis factor-related apoptosis-inducing ligand in vascular inflammation and atherosclerosis: a protector or culprit?
abstract: In addition to inducing tumor cell apoptosis, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows broad biological functions both in vitro and in vivo. TRAIL gene deletion enhanced atherogenesis in hyperlipidemic mice, supporting that endogenous TRAIL has protective actions in maintaining blood vessel homeostasis and repressing atherosclerosis. The mechanisms of this beneficial effect are not understood. It remains to be determined whether the athero-protective action of TRAIL is via direct impacts on residential vascular cells or indirectly by modulating systemic immune functions. However, in vitro experiments indicate that excessive TRAIL may stimulate endothelial cell apoptosis, smooth muscle proliferation and migration, and inflammatory responses. Moreover, TRAIL can stimulate lipid uptake and foam cell formation in cultured macrophages. Here we provide a critical review on the potential relationships between TRAIL and atherosclerosis. We propose that increased TRAIL production may also have potential detrimental effects on vascular inflammation and atherosclerosis. Further in vivo experiments are warranted to elucidate the effects of exogenous TRAIL on atherogenesis.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China. Electronic address: fjiang@sdu.edu.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand
keywords: Atherosclerosis; Death receptors; Immune response; TRAIL; Vascular inflammation