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VPO1 mediates ApoE oxidation and impairs the clearance of plasma lipids

Youfeng Yang1, Zehong Cao, Ling Tian

  • 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

Plos One
|March 2, 2013
PubMed

Insights

Vascular peroxidase 1 (VPO1) oxidizes ApoE, impairing its lipid binding and clearance. This suggests VPO1 is a key factor in lipid metabolism and atherosclerosis development.

Area of Science:

  • Biochemistry
  • Cardiovascular Biology
  • Metabolic Research

Background:

  • Apolipoprotein E (ApoE) is crucial for lipid homeostasis and is implicated in atherosclerosis.
  • Lipoprotein oxidation is a key event in atherosclerosis pathogenesis.
  • Heme-containing peroxidases (hPx), like vascular peroxidase 1 (VPO1), are proposed mediators of lipoprotein oxidation.

Purpose of the Study:

  • To investigate if vascular peroxidase 1 (VPO1) mediates the oxidation of Apolipoprotein E (ApoE).
  • To determine the functional consequences of VPO1-mediated ApoE oxidation on lipid metabolism.

Main Methods:

  • Recombinant ApoE and VPO1 were expressed and purified.
  • ApoE oxidation was induced by VPO1 in the presence of H2O2 and chloride.
  • ApoE oxidation was confirmed using immunoblot and amino acid analyses.
  • Lipid emulsion particle binding and lipid efflux assays were performed.

Main Results:

  • VPO1-oxidized ApoE exhibited weaker binding to lipid emulsion particles.
  • Oxidized ApoE demonstrated reduced lipid efflux capability from foam cells.
  • Mice treated with oxidized ApoE showed impaired plasma lipid clearance.

Conclusions:

  • Vascular peroxidase 1 (VPO1) is identified as a novel mediator of ApoE oxidation.
  • VPO1-mediated ApoE oxidation negatively impacts lipid homeostasis.
  • These findings suggest a significant role for VPO1 in the development of atherosclerosis.
Abstract

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