Low-density lipoprotein modified by myeloperoxidase in inflammatory pathways and clinical studies

Mediators Inflamm. 2013:2013:971579. doi: 10.1155/2013/971579. Epub 2013 Jul 24.

Abstract

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNF α and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apolipoprotein B-100 / metabolism
  • Atherosclerosis
  • Endocytosis
  • Erectile Dysfunction / metabolism
  • Fatty Liver / metabolism
  • Female
  • Fibrinolysis
  • Humans
  • Hydrogen Peroxide / chemistry
  • Inflammation / metabolism*
  • Interleukin-8 / metabolism
  • Lipoproteins, LDL / metabolism*
  • Macrophages / metabolism
  • Male
  • Oxygen / chemistry
  • Peroxidase / metabolism*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Renal Dialysis
  • Sleep Wake Disorders / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Apolipoprotein B-100
  • Interleukin-8
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide
  • Peroxidase
  • Oxygen