Neutrophil Extracellular Trap–Derived Enzymes Oxidize High‐Density Lipoprotein: An Additional Proatherogenic Mechanism in Systemic Lupus Erythematosus

Oxidative stress and oxidized high‐density lipoprotein (HDL) are implicated as risk factors for cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Yet, how HDL is oxidized and rendered dysfunctional in SLE remains unclear. Neutrophil extracellular traps (NETs), the levels of which are elevated in lupus, possess oxidant‐generating enzymes, including myeloperoxidase (MPO), NADPH oxidase (NOX), and nitric oxide synthase (NOS). We hypothesized that NETs mediate HDL oxidation, impairing cholesterol efflux capacity (CEC).

[1]  C. Carmona-Rivera,et al.  Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2 , 2014, Annals of the rheumatic diseases.

[2]  E. Favari,et al.  Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus , 2013, Annals of the rheumatic diseases.

[3]  J. Hodgin,et al.  Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus. , 2013, The Journal of clinical investigation.

[4]  Pojen P. Chen,et al.  NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis , 2013, Science Translational Medicine.

[5]  C. Carmona-Rivera,et al.  Neutrophil Extracellular Trap–Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages , 2013, The Journal of Immunology.

[6]  J. Kahlenberg,et al.  Mechanisms of premature atherosclerosis in rheumatoid arthritis and lupus. , 2013, Annual review of medicine.

[7]  B. Gillespie,et al.  High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis , 2013, Annals of the rheumatic diseases.

[8]  Handong Zheng,et al.  PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures , 2012, Front. Immun..

[9]  A. Koch,et al.  Type I interferons modulate vascular function, repair, thrombosis, and plaque progression in murine models of lupus and atherosclerosis. , 2012, Arthritis and rheumatism.

[10]  D. Wagner,et al.  Neutrophil extracellular trap (NET) impact on deep vein thrombosis. , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[11]  M. Daemen,et al.  Auto-Antigenic Protein-DNA Complexes Stimulate Plasmacytoid Dendritic Cells to Promote Atherosclerosis , 2012, Circulation.

[12]  A. Blom,et al.  Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease , 2012, The Journal of Immunology.

[13]  Oliver Soehnlein,et al.  Multiple roles for neutrophils in atherosclerosis. , 2012, Circulation research.

[14]  W. Koenig,et al.  Myeloperoxidase Production by Macrophage and Risk of Atherosclerosis , 2012, Current Atherosclerosis Reports.

[15]  C. Weber,et al.  Presence of luminal neutrophil extracellular traps in atherosclerosis , 2012, Thrombosis and Haemostasis.

[16]  Werner Solbach,et al.  The Impact of Various Reactive Oxygen Species on the Formation of Neutrophil Extracellular Traps , 2012, Mediators of inflammation.

[17]  S. Pennathur,et al.  Myeloperoxidase Targets Apolipoprotein A-I, the Major High Density Lipoprotein Protein, for Site-Specific Oxidation in Human Atherosclerotic Lesions* , 2012, The Journal of Biological Chemistry.

[18]  Yuan Luo,et al.  The development of N-α-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-α-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors. , 2011, Journal of medicinal chemistry.

[19]  Matthias Kretzler,et al.  Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues, and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus , 2011, The Journal of Immunology.

[20]  U. Švajger,et al.  Mechanism of Endosomal TLR Inhibition by Antimalarial Drugs and Imidazoquinolines , 2011, The Journal of Immunology.

[21]  V. Wahn,et al.  Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. , 2011, Blood.

[22]  Robert L Wilensky,et al.  Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. , 2011, The New England journal of medicine.

[23]  S. Pennathur,et al.  Quantitative analysis of amino Acid oxidation markers by tandem mass spectrometry. , 2011, Methods in enzymology.

[24]  H. Shimokawa,et al.  Pathophysiological relevance of NO signaling in the cardiovascular system: novel insight from mice lacking all NO synthases. , 2010, Pharmacology & therapeutics.

[25]  Roger E Bumgarner,et al.  High-Density Lipoprotein Suppresses the Type I Interferon Response, a Family of Potent Antiviral Immunoregulators, in Macrophages Challenged With Lipopolysaccharide , 2010, Circulation.

[26]  A. Assinger,et al.  Specific binding of hypochlorite-oxidized HDL to platelet CD36 triggers proinflammatory and procoagulant effects. , 2010, Atherosclerosis.

[27]  Abdul Hakkim,et al.  Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis , 2010, Proceedings of the National Academy of Sciences.

[28]  W. Mccune,et al.  A Distinct Subset of Proinflammatory Neutrophils Isolated from Patients with Systemic Lupus Erythematosus Induces Vascular Damage and Synthesizes Type I IFNs , 2010, The Journal of Immunology.

[29]  G. Ferreira,et al.  Increased plasma myeloperoxidase levels in systemic lupus erythematosus , 2010, Rheumatology International.

[30]  M. Wood,et al.  DNase I Inhibits a Late Phase of Reactive Oxygen Species Production in Neutrophils , 2009, Journal of Innate Immunity.

[31]  K. Watson,et al.  Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus. , 2009, Arthritis and rheumatism.

[32]  J. Eiserich,et al.  Plasma levels of myeloperoxidase are not elevated in patients with stable coronary artery disease. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[33]  C. Vahl,et al.  Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intima , 2008, Thrombosis and Haemostasis.

[34]  G. Fonarow,et al.  The paradox of dysfunctional high-density lipoprotein , 2007, Current opinion in lipidology.

[35]  V. Wahn,et al.  Novel cell death program leads to neutrophil extracellular traps. , 2007, The Journal of cell biology.

[36]  M. Diamond,et al.  Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus. , 2006, Biochemistry.

[37]  R. Leboeuf,et al.  Expression of Human Myeloperoxidase by Macrophages Promotes Atherosclerosis in Mice , 2005, Circulation.

[38]  J. Voss,et al.  Tyrosine 192 in Apolipoprotein A-I Is the Major Site of Nitration and Chlorination by Myeloperoxidase, but Only Chlorination Markedly Impairs ABCA1-dependent Cholesterol Transport* , 2005, Journal of Biological Chemistry.

[39]  A. Chait,et al.  Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species* , 2004, Journal of Biological Chemistry.

[40]  K. Griendling,et al.  Giant atrial septal aneurysm simulating a right atrial tumour , 2004, Heart.

[41]  T. Sundqvist,et al.  Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[42]  E J Topol,et al.  Association between myeloperoxidase levels and risk of coronary artery disease. , 2001, JAMA.

[43]  R. Bolli.  Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. , 2001, Journal of molecular and cellular cardiology.

[44]  M. Abrahamowicz,et al.  Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. , 2001, Arthritis and rheumatism.

[45]  J. Heinecke,et al.  Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A-I. , 2001, European journal of biochemistry.

[46]  J. Crowley,et al.  Increased atherosclerosis in myeloperoxidase-deficient mice. , 2001, The Journal of clinical investigation.

[47]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[48]  K. Fong,et al.  Occasional Series: Lupus Around the World Systemic Lupus Erythematosus Research in the Asia-Pacific Region: A co-ordinated and co-operative approach , 1996, Lupus.

[49]  R. Fox,et al.  Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development , 1996, Lupus.

[50]  D. Furst,et al.  Occasional Series: Lupus Around the World Systemic Lupus Erythematosus Research in the Asia-Pacific Region: A co-ordinated and co-operative approach , 1996, Lupus.

[51]  C. Bombardier,et al.  Criteria for assessing disease activity in systemic lupus erythematosus. , 1989, The Journal of rheumatology.