title: VPO1 mediates ApoE oxidation and impairs the clearance of plasma lipids.
abstract: OBJECTIVE
  ApoE is an abundant component of chylomicron, VLDL, IDL, and HDL. It binds to multiple types of lipids and is implicated in cholesterol and triglyceride homeostasis. Oxidation of ApoE plays a crucial role in the genesis of atherosclerosis. It is proposed that heme-containing peroxidases (hPx) are major mediators of lipoprotein oxidization. Vascular peroxidase 1 (VPO1) is a recently-discovered hPx, which is expressed in cardiovascular system, lung, liver etc. and secreted into plasma. Its plasma concentration is three orders of magnitude of that of myeloperoxidase. If VPO1 mediates ApoE oxidation and affects the lipid metabolism remains to be elucidated.
  
  
  METHODS
  Recombinant ApoE and VPO1 were expressed and purified from stably-expressing cell lines deriving from HEK293 cells. ApoE oxidation was carried out by VPO1 in the presence of H2O2 and chloride. ApoE oxidation was verified by a variety of approaches including immunoblot and amino acid analyses. To evaluate the functional changes in VPO1-oxidized ApoE, lipid emulsion particle binding assays were employed.
  
  
  RESULTS
  Oxidized ApoE binds weaker to lipid emulsion particles, which mimic the large lipid complexes in vivo. In lipid efflux assay, oxidized ApoE showed reduced capability in efflux of lipids from foam cells. Mice administrated with oxidized ApoE via blood exhibited weaker clearance ability of plasma lipids.
  
  
  CONCLUSIONS
  Our data suggest that VPO1 is a new mediator regulating lipid homeostasis, implying a role in genesis and development of atherosclerosis.
authors: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors: Youfeng
authors: Y
authors: Yang
authors: Zehong
authors: Z
authors: Cao
authors: Ling
authors: L
authors: Tian
authors: W Timothy
authors: WT
authors: Garvey
authors: Guangjie
authors: G
authors: Cheng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D005487:Foam Cells / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D000097423:Peroxidasin
chemical_list: D001057:Apolipoproteins E; D002784:Cholesterol; D006861:Hydrogen Peroxide; D008055:Lipids; D010544:Peroxidases; D011994:Recombinant Proteins; D014280:Triglycerides; C535215:PXDN protein, human; D000097423:Peroxidasin; C535216:Pxdn protein, mouse