title: Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.
abstract: BACKGROUND
  High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO2-oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects.
  
  
  METHODS
  Here we determined the effects of NO2-oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model.
  
  
  RESULTS
  Our results showed that native HDL promoted SMC proliferation and migration, whereas NO2-oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO2-oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO2-oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO2-oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO2-oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque.
  
  
  CONCLUSIONS
  These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI.
authors.affiliation: Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
authors.forename: Boda
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zu
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, Deyang, 618000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department Biochemistry & Molecular Biology, the University of Calgary, Alberta, Canada.
authors.forename: Xilong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Enchen
authors.initials: E
authors.lastname: Zhou
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. zhengl@bjmu.edu.cn.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China. weigao@bjmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D054879:Halogenation; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
chemical_list: D008075:Lipoproteins, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D009195:Peroxidase
keywords: Atherosclerosis; HDL; MPO; Migration; Proliferation; Protein kinases/MAP kinase; Smooth muscle cell