VPO1 mediates oxidation of LDL and formation of foam cells.

Youfeng Yang,Guogang Zhang,Ruizheng Shi,Guangjie Cheng,Zehong Cao

doi:10.18632/oncotarget.9193

Youfeng Yang, Guogang Zhang + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.9193

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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.

Highlights

Atherosclerosis is a multistep, multifactorial and inflammatory disease, characterized by deposition of lipoprotein, monocyte recruitment, and formation of foam cells in arterial walls [1,2,3]
Vascular peroxidase-1 (VPO1) is unique in heme-containing peroxidase (hPx) family; it contains five leucine-rich repeats (LRRs) and four immunoglobulin (Ig) C2 domains at the N-terminus [17]
The pull-down experiments showed that fulllength VPO1 and VPO1 29-250 aa, not VPO1 251-609aa, bound to low-density lipoprotein (LDL)

Summary

Introduction

Atherosclerosis is a multistep, multifactorial and inflammatory disease, characterized by deposition of lipoprotein, monocyte recruitment, and formation of foam cells in arterial walls [1,2,3]. Oxidation of low-density lipoprotein (LDL) plays an important role both in lesion initiation and progression. Oxidized LDL (oxLDL) in arterial walls is considered as one of the major onset mechanisms for the pathogenesis of atherosclerosis [7]. MPO-transgenic mice, whose macrophages www.impactjournals.com/oncotarget expressed human MPO, revealed more severe lesion of atherosclerosis [15]. These data imply a role for another (non-MPO) heme-containing peroxidase (hPx) in arterial walls in the pathogenesis of atherosclerosis

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