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学科主题: 基础医学
题名:
High-density lipoprotein nitration and chlorination catalyzed by myeloperoxidase impair its effect of promoting endothelial repair
作者: Pan, Bing1,2,3; Yu, Baoqi1,2,3; Ren, Hui1,2,3; Willard, Belinda4; Pan, Ling5; Zu, Lingyun6; Shen, Xiaoli5; Ma, Yijing1,2,3; Li, Xiuli7; Niu, Chenguang1,2,3; Kong, Jinge1,2,3; Kang, Siyu1,2,3; Chen, Y. Eugene; Pennathur, Subramaniam8; Zheng, Lemin1,2,3
关键词: HDL ; MPO ; Oxidation ; Endothelial cell ; Migration ; Free radicals
刊名: FREE RADICAL BIOLOGY AND MEDICINE
发表日期: 2013-07-01
DOI: 10.1016/j.freeradbiomed.2013.02.004
卷: 60, 页:272-281
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism
研究领域[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism
关键词[WOS]: APOLIPOPROTEIN-A-I ; NITRIC-OXIDE SYNTHASE ; FIBROBLAST GROWTH-FACTOR ; SCAVENGER RECEPTOR-BI ; PROGENITOR CELLS ; HYPOCHLORITE-MODIFICATION ; PROTEIN-PHOSPHORYLATION ; CARDIOVASCULAR-DISEASE ; CHOLESTEROL EFFLUX ; MASS-SPECTROMETRY
英文摘要:

High-density lipoprotein (HDL) plays a key role in protecting against atherosclerosis. In cardiovascular disease, HDL can be nitrated and chlorinated by myeloperoxidase (MPO). In this study, we discovered that MPO-oxidized HDL is dysfunctional in promoting endothelial repair compared to normal HDL. Proliferation assay, wound healing, and transwell migration experiments showed that MPO-oxidized HDL was associated with a reduced stimulation of endothelial cell (EC) proliferation and migration. In addition, we found that Akt and ERK1/2 phosphorylation in ECs was significantly lower when ECs were incubated with oxidized HDL compared with normal HDL. To further determine whether oxidized HDL diminished EC migration through the PI3K/Akt and MEK/ERK pathways, we performed experiments with inhibitors of both these pathways. The transwell experiments performed in the presence of these inhibitors showed that the migration capacity was reduced and the differences observed between normal HDL and oxidized HDL were diminished. Furthermore, to study the effects of oxidized HDL on endothelial cells in vivo, we performed a carotid artery electric injury model on nude mice injected with either normal or oxidized HDL. Oxidized HDL inhibited reendothelialization compared to normal HDL in vivo. These findings implicate a key role for MPO-oxidized HDL in the pathogenesis of cardiovascular disease. (C) 2013 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 2010CB912504 ; 2011CB503900 ; 30900595 ; 30821001 ; 81172500 ; 81170101 ; 7102104 ; 7122106 ; 2009J01112 ; 20090001120039 ; 20100001120034
项目资助者: "973" National ST Major Project ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; Natural Science Foundation of Fujian ; State Education Ministry of China ; University of Michigan-Peking University Health Science Center Joint Institute
WOS记录号: WOS:000319486500030
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61938
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Cleveland Clin, Prote Lab, Cleveland, OH 44195 USA
2.Peking Univ Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
3.Peking Univ Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100191, Peoples R China
4.Peking Univ Hlth Sci Ctr, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Minist Hlth, Beijing 100191, Peoples R China
5.Fujian Prov Hosp, Fujian Key Lab Cardiovasc Dis, Fuzhou 350001, Peoples R China
6.Peking Univ Third Hosp, Dept Cardiovasc Med, Beijing 100191, Peoples R China
7.Chinese Peoples Liberat Army Gen Hosp, Dept Gynecol & Obstet, Beijing 100853, Peoples R China
8.Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA

Recommended Citation:
Pan, Bing,Yu, Baoqi,Ren, Hui,et al. High-density lipoprotein nitration and chlorination catalyzed by myeloperoxidase impair its effect of promoting endothelial repair[J]. FREE RADICAL BIOLOGY AND MEDICINE,2013,60:272-281.
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