Full Text

Turn on search term navigation

© 2013 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
VPO1 Mediates ApoE Oxidation and Impairs the Clearance of Plasma Lipids
Author
Yang, Youfeng; Cao, Zehong; Tian, Ling; Garvey, W Timothy; Cheng, Guangjie
First page
e57571
Section
Research Article
Publication year
2013
Publication date
Feb 2013
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1351902117
Copyright
© 2013 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.