title: Hypercysteinemia promotes atherosclerosis by reducing protein S-nitrosylation.
abstract: Protein S-nitrosylation plays important role in the regulation of cardiovascular functions in nitric oxide (NO) Pathway. Hypercysteinemia (HHcy) is an independently risk factor for atherosclerosis. We hypothesized that HHcy promotes atherosclerosis by reducing level of vascular protein S-nitrosylation. The aim of present study is to investigate effect of HHcy on vascular protein S-nitrosylation. A total of 45 male apoE-/- mice were randomly divided into three groups. The control group was fed a Western-type diet. The HHcy group was fed a diet containing 4.4% L-methionine, and the HHcy+NONOate group was fed a diet containing 4.4% L-methionine and administrated NONOate (ip). Human umbilical vein endothelial cells were performed for in vitro experiment. Plasma lipids were measured every 4 weeks. After 12 weeks, aortic atherosclerotic lesion areas were detected as well as cellular components. The levels of plasma homocysteine (Hcy) and NO were measured. S-nitrosylation was detected using immunofluorescence, and further confirmed by biotin switch method. We found that compared with the control group, Hcy levels, and atherosclerotic plaque, and content of vascular smooth muscle cells and macrophages in lesions significantly increased, and levels of NO significantly decreased in the HHcy group. However, NONOate reverses this effect. In addition, Hcy significantly reduced protein S-nitrosylation in human umbilical vein endothelial cells. This reduction of protein S-nitrosylation was accompanied by reduced levels of NO. Our results suggested that Hcy promoted atherosclerosis by inhibiting vascular protein S-nitrosylation.
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi, 710061, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi, 710061, China.
authors.forename: Ruihan
authors.initials: R
authors.lastname: Liu
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: The Third People's Hospital of Kunshan, Suzhou, Jiangsu 215316, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi, 710061, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, BMC A13, SE-221 84 Lund, Sweden.
authors.forename: Cangbao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, BMC A13, SE-221 84 Lund, Sweden.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi, 710061, China. Electronic address: liuenqi@hotmail.com.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017293:Protein S / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017293:Protein S; D009569:Nitric Oxide
keywords: Atherosclerosis; Hypercysteinemia; Nitric oxide; S-nitrosylation