Oxidized phospholipids as modulators of inflammation in atherosclerosis

Current Opinion in Lipidology

Volumn 14, Issue 5, 2003, Pages 421-430

  Leitinger, Norbert ^a  

^a UNIVERSITY OF VIENNA   (Austria)

Author keywords

Apoptosis; Atherosclerosis; Free radicals; Host defense; Inflammation; Oxidized phospholipids; Signal transduction

Indexed keywords

1 PALMITOYL 2 (5 OXOVALEROYL)GLYCERO 3 PHOSPHORYLCHOLINE; 1 PALMITOYL 2 GLUTAROYLGLYCERO 3 PHOSPHORYLCHOLINE; CYCLOOXYGENASE 2; EARLY GROWTH RESPONSE FACTOR 1; EPOXYISOPROSTANE; GLUTATHIONE; HEME OXYGENASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIPOPOLYSACCHARIDE; PHOSPHOLIPID; THROMBOMODULIN; THROMBOPLASTIN; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ACUTE DISEASE; AORTA; APOPTOSIS; ARTERY ENDOTHELIUM; ATHEROGENESIS; ATHEROSCLEROSIS; CELL ADHESION; CELL PROTECTION; CHEMICAL STRUCTURE; CHRONIC DISEASE; DISEASE ACTIVITY; ENDOTHELIUM CELL; GENE EXPRESSION; GENETIC ANALYSIS; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INHIBITION KINETICS; LIPID ANALYSIS; LIPID OXIDATION; LIPID PEROXIDATION; MOLECULAR RECOGNITION; NONHUMAN; PLASMA; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS;

ANIMALS; APOPTOSIS; ARTERIOSCLEROSIS; DNA-BINDING PROTEINS; EARLY GROWTH RESPONSE PROTEIN 1; GENE EXPRESSION REGULATION; HUMANS; IMMEDIATE-EARLY PROTEINS; INFLAMMATION; LIPOPOLYSACCHARIDES; NF-KAPPA B; OXIDATION-REDUCTION; PHOSPHATIDYLCHOLINES; PHOSPHOLIPIDS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 0142124855     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/00041433-200310000-00002     Document Type: Review

References (83)

1. Berliner J. Introduction: lipid oxidation products and atherosclerosis. Vascul Pharmacol 2002; 38:187-191.
2. Navab M, Hama SY, Ready ST, et al. Oxidized lipids as mediators of coronary heart disease. Curr Opin Lipidol 2002; 13:363-372.
3. Watson AD, Leitinger N, Navab M, et al. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem 1997; 272:13597-13607.
4. Watson AD, Subbanagounder G, Welsbie DS, et al. Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. J Biol Chem 1999; 274:24787-24798.
5. Ahmed Z, Babaei S, Maguire GF, et al. Paraoxonase-1 reduces monocyte chemotaxis and adhesion to endothelial cells due to oxidation of palmitoyl, linoleoyl glycerophosphorylcholine. Cardiovasc Res 2003; 57:225-231.
6. Podrez EA, Poliakov E, Shen Z, et al. Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36. J Biol Chem 2002; 277:38503-38516. This is a detailed study in which the authors structurally identify phospholipid oxidation products derived from PAPC and PLPC, using a myeloperoxidase-dependent oxidation system. Furthermore, structural requirements for high-affinity binding of these newly identified lipids to CD36 are characterized.
7. Podrez EA, Poliakov E, Shen Z, et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem 2002; 277:38517-38523.
8. Hoff HF, O'Neil J, Wu Z, et al. Phospholipid hydroxyalkenals: biological and chemical properties of specific oxidized lipids present in atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2003; 23:275-282.
9. Subbanagounder G, Deng Y, Borromeo C, et al. Hydroxy alkenal phospholipids regulate inflammatory functions of endothelial cells. Vascul Pharmacol 2002; 38:201-209.
10. Subbanagounder G, Wong JW, Lee H, et al. Epoxyisoprostane and epoxycyclopentenone phospholipids regulate monocyte chemotactic protein-1 and interleukin-8 synthesis: formation of these oxidized phospholipids in response to interleukin-1beta. J Biol Chem 2002; 277:7271-7281. The authors describe biological activities of new oxidized phospholipids. They show that isomers of epoxyisoprostane and epoxycyclopentenone induce MCP-1 and IL-8 expression via PPARa in endothelial cells. Furthermore, this is one of the few reports demonstrating the generation of oxidized phospholipids as a result of inflammation-induced oxidative stress.
11. Prescott SM, McIntyre TM, Zimmerman GA, Stafforini DM. Sol Sherry lecture in thrombosis: molecular events in acute inflammation. Arterioscler Thromb Vasc Biol 2002; 22:727-733.
12. McIntyre TM, Zimmerman GA, Prescott SM. Biologically active oxidized phospholipids. J Biol Chem 1999; 274:25189-25192.
13. Prescott SM, Zimmerman GA, Stafforini DM, McIntyre TM. Platelet-activating factor and related lipid mediators. Annu Rev Biochem 2000; 69:419-445.
14. Marathe GK, Davies SS, Harrison KA, et al. Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J Biol Chem 1999; 274:28395-28404.
15. Marathe GK, Zimmerman GA, Prescott SM, McIntyre TM. Activation of vascular cells by PAF-like lipids in oxidized LDL. Vascul Pharmacol 2002; 38:193-200.
16. Leitinger N, Watson AD, Faull KF, et al. Monocyte binding to endothelial cells induced by oxidized phospholipids present in minimally oxidized low density lipoprotein is inhibited by a platelet activating factor receptor antagonist. Adv Exp Med Biol 1997; 433:379-382.
17. Subbanagounder G, Leitinger N, Schwenke DC, et al. Determinants of bioactivity of oxidized phospholipids: specific oxidized fatty acyl groups at the sn-2 position. Arterioscler Thromb Vasc Biol 2000; 20:2248-2254.
18. Subbanagounder G, Leitinger N, Shih PT, et al. Evidence that phospholipid oxidation products and/or platelet-activating factor play an important role in early atherogenesis: in vitro and in vivo inhibition by WEB 2086. Circ Res 1999; 85:311-318.
19. Subbanagounder G, Watson AD, Berliner JA. Bioactive products of phospholipid oxidation: isolation, identification, measurement and activities. Free Radic Biol Med 2000; 28:1751-1761.
20. Parhami F, Fang ZT, Yang B, et al. Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized LDL. Arterioscler Thromb Vasc Biol 1995; 15:2019-2024.
21. Kamido H, Eguchi H, Ikeda H, et al. Core aldehydes of alkyl glyceropho-sphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation. J Lipid Res 2002; 43:158-166.
22. Berliner JA, Subbanagounder G, Leitinger N, et al. Evidence for a role of phospholipid oxidation products in atherogenesis. Trends Cardiovasc Med 2001; 11:142-147.
23. Podrez EA, Abu-Soud HM, Hazen SL. Myeloperoxidase-generated oxidants and atherosclerosis. Free Radic Biol Med 2000; 28:1717-1725.
24. Savenkova ML, Mueller DM, Heinecke JW. Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein. J Biol Chem 1994; 269:20394-20400.
25. Podrez EA, Schmitt D, Hoff HF, Hazen SL. Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest 1999; 103:1547-1560.
26. Schmitt D, Shen Z, Zhang R, et al. Leukocytes utilize myeloperoxidase-generated nitrating intermediates as physiological catalysts for the generation of biologically active oxidized lipids and sterols in serum. Biochemistry 1999; 38:16904-16915.
27. Zhang R, Brennan ML, Shen Z, et al. Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 2002; 277:46116-46122. In this paper the authors prove the hypothesis that myeloperoxidase is a major enzyme involved in lipid oxidation at sites of inflammation in vivo. Using myeloperoxidase null mice, they show that lipid oxidation was reduced by 85%.
28. Zhang R, Shen Z, Nauseef WM, Hazen SL. Defects in leukocyte-mediated initiation of lipid peroxidation in plasma as studied in myeloperoxidase- deficient subjects: systematic identification of multiple endogenous diffusible substrates for myeloperoxidase in plasma. Blood 2002; 99:1802-1810.
29. Lang JD, McArdle PJ, O'Reilly PJ, Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002; 122:314-320.
30. Wood LG, Gibson PG, Garg ML. Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur Respir J 2003; 21:177-186.
31. Uhlson C, Harrison K, Allen CB, et al. Oxidized phospholipids derived from ozone-treated lung surfactant extract reduce macrophage and epithelial cell viability. Chem Res Toxicol 2002; 15:896-906.
32. Nakamura T, Henson PM, Murphy RC. Occurrence of oxidized metabolites of arachidonic acid esterified to phospholipids in murine lung tissue. Anal Biochem 1998; 262:23-32.
33. Matot I, Manevich Y, Al Mehdi AB, et al. Fluorescence imaging of lipid peroxidation in isolated rat lungs during nonhypoxic lung ischemia. Free Radic Biol Med 2003; 34:785-790.
34. Albert CJ, Thukkani AK, Heuertz RM, et al. Eosinophil peroxidase-derived reactive brominating species target the vinyl ether bond of plasmalogens generating a novel chemoattractant, alpha-bromo fatty aldehyde. J Biol Chem 2003; 278:8942-8950.
35. Silva AR, de Assis EF, Caiado LF, et al. Monocyte chemoattractant protein-1 and 5-lipoxygenase products recruit leukocytes in response to platelet-activating factor-like lipids in oxidized low-density lipoprotein. J Immunol 2002; 168:4112-4120. One mechanism by which oxidized phospholipids induce leukocyte accumulation in vivo is described in this paper. Inflammation induced by PAF-like lipids in the pleural cavity of mice was dependent on MCP-1 production and activation of the 5-iipoxygenase pathway, resulting in leukotriene B4 production.
36. Lloberas N, Torras J, Herrero-Fresneda I, et al. Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids: prevention by antioxidant treatment. FASEB J 2002; 16:908-910. In this study it is shown that oxidized phospholipids are produced during ischemia and play a role in inflammation in the kidney.
37. Lloberas N, Torras J, Herrero I, et al. The ether phospholipids trail: blood timing in renal ischemia-reperfusion injury. Transplant Proc 2002; 34:47-48.
38. Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003; 41:360-370.
39. Frey B, Johnen W, Haupt R, et al. Bioactive oxidized lipids in the plasma of cardiac surgical intensive care patients. Shock 2002; 18:14-17.
40. Frey B, Haupt R, Alms S, et al. Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress. J Lipid Res 2000; 41:1145-1153.
41. Sampson MJ, Gopaul N, Davies IR, et al. Plasma F2 isoprostanes: direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes. Diabetes Care 2002; 25:537-541.
42. Lehr HA, Weyrich AS, Saetzler RK, et al. Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking. J Clin Invest 1997; 99:2358-2364.
43. 2, platelet activating factor-acetylhydrolase. Atheroscler Suppl 2002; 3:57-68.
44. Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 2002; 30:294-301. This is a comprehensive review about the role of PAF and PAF-like lipids in settings of general inflammatory disorders.
45. Ahmed Z, Ravandi A, Maguire GF, et al. Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. Biochem Biophys Res Commun 2002; 290:391-396.
46. Arai H. Platelet-activating factor acetylhydrolase. Prostaglandins Other Lipid Mediat 2002; 68-69:83-94.
47. Forte TM, Subbanagounder G, Berliner JA, et al. Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice. J Lipid Res 2002; 43:477-485.
48. Kadl A, Huber J, Gruber F, et al. Analysis of inflammatory gene induction by oxidized phospholipids in vivo by quantitative real-time RT-PCR in comparison with effects of LPS. Vascul Pharmacol 2002; 38:219-227.
49. 2SO-differentiated HL-60 cells: role in phagocytic clearance. J Biol Chem 2002; 277:49965-49975. Here the authors show that during apoptosis NADPH oxidase is the major enzyme triggering phospholipid oxidation.
50. Tyurina YY, Tyurin VA, Shvedova AA, et al. Peroxidation of phosphatidylserine in mechanisms of apoptotic signaling. Methods Enzymol 2002; 352:159-174.
51. Shvedova AA, Tyurina JY, Kawai K, et al. Selective peroxidation and externalization of phosphatidylserine in normal human epidermal keratinocytes during oxidative stress induced by cumene hydroperoxide. J Invest Dermatol 2002; 118:1008-1018.
52. Kagan VE, Fabisiak JP, Shvedova AA, et al. Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis. FEBS Lett 2000; 477:1-7.
53. Kagan VE, Gleiss B, Tyurina YY, et al. A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis. J Immunol 2002; 169:487-499.
54. Chang MK, Bergmark C, Laurila A, et al. Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition. Proc Natl Acad Sci U S A 1999; 96:6353-6358.
55. Chang MK, Binder CJ, Torzewski M, Witztum JL. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A 2002; 99:13043-13048. In this paper C-reactive protein is described as an oxidized phospholipid recognizing receptor.
56. Huber J, Vales A, Mitulovic G, et al. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler Thromb Vasc Biol 2002; 22:101-107. Additional sources for oxidized phospholipids are described in this paper.
57. Patel KD, Zimmerman GA, Prescott SM, McIntyre TM. Novel leukocyte agonists are released by endothelial cells exposed to peroxide. J Biol Chem 1992; 267:15168-15175.
58. Parhami F, Fang ZT, Fogelman AM, et al. Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. J Clin Invest 1993; 92:471-478.
59. Bochkov VN, Mechtcheriakova D, Lucerna M, et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT. Blood 2002; 99:199-206. In this paper, signaling pathways are described that are induced by oxidized phospholipids and lead to expression of the tissue factor gene in endothelial cells. It is clearly demonstrated that the NFκB pathway is not induced by oxidized phospholipids.
60. Reddy S, Hama S, Grijalva V, et al. Mitogen-activated protein kinase phosphatase 1 activity is necessary for oxidized phospholipids to induce monocyte chemotactic activity in human aortic endothelial cells. J Biol Chem 2001; 276:17030-17035.
61. Lee H, Shi W, Tontonoz P, et al. Role for peroxisome proliferator- activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 2000; 87:516-521.
62. 2-dependent manner. FEBS Lett 2000; 471:34-38.
63. Davies SS, Pontsler AV, Marathe GK, et al. Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists. J Biol Chem 2001; 276:16015-16023.
64. Gimbrone Jr MA, Cybulsky MI, Kume N, et al. Vascular endothelium: an integrator of pathophysiological stimuli in atherogenesis. Ann NY Acad Sci 1995; 748:122-131.
65. Pontsler AV, St Hilaire A, Marathe GK, et al. Cyclooxygenase-2 is induced in monocytes by peroxisome proliferator activated receptor gamma and oxidized alkyl phospholipids from oxidized low density lipoprotein. J Biol Chem 2002; 277:13029-13036.
66. Cui MZ, Penn MS, Chisolm GM. Native and oxidized low density lipoprotein induction of tissue factor gene expression in smooth muscle cells is mediated by both Egr-1 and Sp1. J Biol Chem 1999; 274:32795-32802.
67. Ishii H, Tezuka T, Ishikawa H, et al. Oxidized phospholipids in oxidized low-density lipoprotein downregulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RAR{beta}-RXR{alpha} heterodimers and Sp1 and 3 to their binding sequences in the TM promoter. Blood 2003; 101:4765-4774. In this study the authors describe a mechanism by which oxidized phospholipids can induce the downregulation of gene expression.
68. Li N, Venkatesan MI, Miguel A, et al. Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J Immunol 2000; 165:3393-3401.
69. Reddy ST, Grijalva V, Ng C, et al. Identification of genes induced by oxidized phospholipids in human aortic endothelial cells. Vascul Pharmacol 2002; 38:211-218. This is the first study screening for genes that are induced by OxPAPC.
70. Van Lenten BJ, Wagner AC, Navab M, Fogelman AM. Oxidized phospholipids induce changes in hepatic paraoxonase and ApoJ but not monocyte chemoattractant protein-1 via interleukin-6. J Biol Chem 2001; 276:1923-1929.
71. Penn MS, Cui MZ, Winokur AL, et al. Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation. Blood 2000; 96:3056-3063.
72. Ishikawa K, Navab M, Leitinger N, et al. Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL. J Clin Invest 1997; 100:1209-1216.
73. 2 secretion in skin. The immunosuppressive action of ultraviolet radiation is explained by the formation of phospholipid oxidation products.
74. Moellering DR, Levonen AL, Go YM, et al. Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress. Biochem J 2002; 362:51-59. In this paper it is shown that OxPAPC also induces cytoprotective mechanisms by the upregulation of glutathione synthesis.
75. Eligini S, Brambilla M, Banfi C, et al. Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-kappaB/IkappaB- and ERK2-dependent mechanisms. Cardiovasc Res 2002; 55:406-415.
76. Morse D, Choi AM. Heme oxygenase-1: the 'emerging molecule' has arrived. Am J Respir Cell Mol Biol 2002; 27:8-16.
77. Otterbein LE, Zuckerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 2003; 9:183-190.
78. Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000; 6:422-428.
79. Ryter SW, Otterbein LE, Morse D, Choi AM. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 2002; 234-235:249-263.
80. Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002; 8:240-246.
81. Wagener FA, Van Beurden HE, Von Den Hoff JW, et al. The heme-heme oxygenase system: a molecular switch in wound healing. Blood 2003; 102:521-528.
82. Leitinger N, Tyner TR, Oslund L, et al. Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc Natl Acad Sci U S A 1999; 96:12010-12015.
83. Bochkov VN, Kadi A, Huber J, et al. Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 2002; 419:77-81. In this study the authors demonstrate a mechanism by which lipopolysaccharide- induced inflammation is inhibited by oxidized phospholipids. They hypothesize that the formation of phospholipid oxidation products during bacterial infection may interfere with innate immune reactions during host defence.