title: A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury.
abstract: 5-Methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, was recently shown to suppress inflammatory mediator-induced cancer cell proliferation and migration. However, the role of 5-MTP in vascular disease is unknown. In this study, we investigated whether 5-MTP protects against vascular remodeling following arterial injury. Measurements of serum 5-MTP levels in healthy subjects and patients with coronary artery disease (CAD) showed that serum 5-MTP concentrations were inversely correlated with CAD. To test the role of 5-MTP in occlusive vascular disease, we subjected mice to a carotid artery ligation model of neointima formation and treated mice with vehicle or 5-MTP. Compared with vehicle-treated mice, 5-MTP significantly reduced intimal thickening by 40% 4 weeks after ligation. BrdU incorporation assays revealed that 5-MTP significantly reduced VSMC proliferation both in vivo and in vitro. Furthermore, 5-MTP reduced endothelial loss and detachment, ICAM-1 and VCAM-1 expressions, and inflammatory cell infiltration in the ligated arterial wall, suggesting attenuation of endothelial dysfunction. Signaling pathway analysis indicated that 5-MTP mediated its effects predominantly via suppressing p38 MAPK signaling in endothelial and VSMCs. Our data demonstrate a novel vascular protective function of 5-MTP against arterial injury-induced intimal hyperplasia. 5-MTP might be a therapeutic target for preventing and/or treating vascular remodeling.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Ho
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Wu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chen-Hsuan
authors.initials: CH
authors.lastname: Su
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chung-Huang
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Hua-Hui
authors.initials: HH
authors.lastname: Ho
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Guan-Lin
authors.initials: GL
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Wei-Shiang
authors.initials: WS
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Yu-Juei
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|Metabolomic Research Center and Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|Metabolomic Research Center and Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Department of Medical Sciences and Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.|Metabolomic Research Center and Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Shaw-Fang
authors.initials: SF
authors.lastname: Yet
mesh_terms: D000368:Aged; D000818:Animals; D001158:Arteries / Q000293:injuries*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy*; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C027986:5-methoxytryptophan; D014364:Tryptophan