title: VPO1 mediates oxidation of LDL and formation of foam cells.
abstract: Deposition of oxidized-LDL in vascular walls is essential in the initiation of atherosclerosis. Oxidation of LDL has been attributed to myeloperoxidase as its generation of potent oxidants. However, the exact mechanism of LDL oxidation and foam cell formation in atherosclerosis remains to be elucidated. Vascular peroxidase-1 (VPO1), a newly-identified heme-containing peroxidase, is primarily expressed in cardiovascular systems, and secreted into the circulation. The present study evaluates VPO1-mediated LDL oxidation and its role in atherosclerosis. VPO1 was first demonstrated binding to LDL. VPO1-mediated oxidation of proteins and lipids in LDL was verified by a variety of methods including immunoblot analysis, free tryptophan assay, UV absorbance, and thiobarbituric acid assay. VPO1-oxidized LDL caused accumulation of LDL in monocyte-like cells and promoted formation of foam cells. Administration of inflammation factors, LPS or TNF-α, induced increasing expression of VPO1 in aorta and secretion to plasma. TNF-α also promoted formation and retention of VPO1-oxidized LDL in aortic walls. Our data suggest that VPO1 contributes to oxidation and retention of LDL in vessel walls, and formation foam cells, indicating VPO1 as a novel potential mediator of atherosclerosis.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Youfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.|Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ruizheng
authors.initials: R
authors.lastname: Shi
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Zehong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D013858:Thiobarbiturates / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097423:Peroxidasin
chemical_list: D006997:Hypochlorous Acid; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D010544:Peroxidases; D013858:Thiobarbiturates; D014364:Tryptophan; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; C535215:PXDN protein, human; D000097423:Peroxidasin; C535216:Pxdn protein, mouse; C029684:thiobarbituric acid
keywords: Gerotarget; foam cells; free radical; heme-containing peroxidase; low-density lipoprotein; oxidized lipids