title: N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein.
abstract: Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR(-/-)) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR(-/-) mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia.
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.|Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, USA.
authors.forename: Chandrakala A
authors.initials: CA
authors.lastname: Narasimhulu
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Patrick Z
authors.initials: PZ
authors.lastname: Liu
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Hao
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xie
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Lianqun
authors.initials: L
authors.lastname: Cui
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, USA.
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D000111:Acetylcysteine