Role of phospholipid oxidation products in atherosclerosis

Circulation Research

Volumn 111, Issue 6, 2012, Pages 778-799

  Lee, Sangderk ^a   Birukov, Konstantin G ^c   Romanoski, Casey E ^b   Springstead, James R ^b   Lusis, Aldons J ^b   Berliner, Judith A ^a,b  

^a Department of Pathology ^*  (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

Author keywords

atherosclerosis; inflammation; Ox PAPC; phospholipids

Indexed keywords

CD36 ANTIGEN; EPIDERMAL GROWTH FACTOR RECEPTOR; FATTY ACID; HIGH DENSITY LIPOPROTEIN; INTERLEUKIN 8; MEMBRANE PROTEIN; OXIDIZED LOW DENSITY LIPOPROTEIN; PHOSPHATIDYLCHOLINE; PHOSPHOLIPID; PHOSPHOLIPID OXIDATION PRODUCT; PROSTAGLANDIN E RECEPTOR 2; SCAVENGER RECEPTOR BI; STEROL REGULATORY ELEMENT BINDING PROTEIN; THROMBOCYTE ACTIVATING FACTOR RECEPTOR; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR NRF2; TRANSMEMBRANE PROTEIN 30A; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; APOPTOSIS; ATHEROGENESIS; ATHEROSCLEROSIS; BLOOD VESSEL WALL; CELL DIVISION; COVALENT BOND; CYTOKINE PRODUCTION; ENDOCYTOSIS; ENDOTHELIUM CELL; FOAM CELL; GENE CONTROL; GENETIC TRANSCRIPTION; HUMAN; LIPID OXIDATION; MACROPHAGE; MONOCYTE; NONHUMAN; NUCLEAR OVERHAUSER EFFECT; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; THROMBOCYTE; THROMBOCYTE ACTIVATION; THROMBOSIS; UNFOLDED PROTEIN RESPONSE;

ATHEROSCLEROSIS; CYTOKINES; ENDOTHELIAL CELLS; HUMANS; MACROPHAGES; MYOCYTES, SMOOTH MUSCLE; OXIDATION-REDUCTION; PHOSPHOLIPIDS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 84865835473     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.111.256859     Document Type: Review

References (138)

1. Berliner JA, Leitinger N, Tsimikas S. The role of oxidized phospholipids in atherosclerosis. J Lipid Res. 2009;50(Suppl):S207-S212.
2. Bochkov VN, Oskolkova OV, Birukov KG, Levonen AL, Binder CJ, Stockl J. Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal. 2010;12:1009-1059.
3. Hahn BH, McMahon M. Atherosclerosis and systemic lupus erythematosus: the role of altered lipids and of autoantibodies. Lupus. 2008;17: 368-370.
4. Tsimikas S, Mallat Z, Talmud PJ, Kastelein JJ, Wareham NJ, Sandhu MS, Miller ER, Benessiano J, Tedgui A, Witztum JL, Khaw KT, Boekholdt SM. Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol. 2010;56: 946-955.
5. Choi SH, Chae A, Miller E, Messig M, Ntanios F, DeMaria AN, Nissen SE, Witztum JL, Tsimikas S. Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the reversal (reversal of atherosclerosis with aggressive lipid lowering) study. J Am Coll Cardiol. 2008;52:24-32.
6. Fraley AE, Schwartz GG, Olsson AG, Kinlay S, Szarek M, Rifai N, Libby P, Ganz P, Witztum JL, Tsimikas S. Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: results from the miracl (myocardial ischemia reduction with aggressive cholesterol lowering) trial. J Am Coll Cardiol. 2009;53:2186-2196.
7. Tsimikas S, Aikawa M, Miller FJ Jr, Miller ER, Torzewski M, Lentz SR, Bergmark C, Heistad DD, Libby P, Witztum JL. Increased plasma oxidized phospholipid:apolipoprotein b-100 ratio with concomitant depletion of oxidized phospholipids from atherosclerotic lesions after dietary lipid-lowering: a potential biomarker of early atherosclerosis regression. Arterioscler Thromb Vasc Biol. 2007;27:175-181.
8. Podrez EA, Byzova TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, Hazen SL. Platelet cd36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nature medicine. 2007;13: 1086-1095.
9. Nicholls SJ, Hazen SL. Myeloperoxidase, modified lipoproteins, and atherogenesis. J Lipid Res. 2009;50(Suppl):S346-S351.
10. Cyrus T, Pratico D, Zhao L, Witztum JL, Rader DJ, Rokach J, FitzGerald GA, Funk CD. Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice. Circulation. 2001;103:2277-2282.
11. Van Lenten BJ, Wagner AC, Jung CL, Ruchala P, Waring AJ, Lehrer RI, Watson AD, Hama S, Navab M, Anantharamaiah GM, Fogelman AM. Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I. J Lipid Res. 2008;49: 2302-2311.
12. Friedman P, Horkko S, Steinberg D, Witztum JL, Dennis EA. Correlation of antiphospholipid antibody recognition with the structure of synthetic oxidized phospholipids. Importance of schiff base formation and aldol condensation. J Biol Chem. 2002;277:7010-7020.
13. Boullier A, Friedman P, Harkewicz R, Hartvigsen K, Green SR, Almazan F, Dennis EA, Steinberg D, Witztum JL, Quehenberger O. Phosphocholine as a pattern recognition ligand for cd36. J Lipid Res. 2005;46:969-976.
14. Greenberg ME, Sun M, Zhang R, Febbraio M, Silverstein R, Hazen SL. Oxidized phosphatidylserine-cd36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J Exp Med. 2006;203:2613-2625.
15. Salomon RG. Forum review-levuglandins and isolevuglanins: Stealthy toxins of oxidative injury. Antioxid Redox Signal. 2005;7:185-201.
16. Salomon RG, Hong L, Hollyfield JG. Discovery of carboxyethylpyrroles (CEPS): critical insights into amd, autism, cancer, and wound healing from basic research on the chemistry of oxidized phospholipids. Chem Res Tox. 2011;24:1803-1816.
17. Lee S, Springstead JR, Parks B, Romanoski CE, Palvolgyi R, Ho T, Nguyen P, Lusis AJ, Berliner JA. Metalloproteinase processing of hbegf is a proximal event in the response of human aortic endothelial cells to oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2012; 32:1246-1254.
18. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204-212.
19. Weismann D, Binder CJ. The innate immune response to products of phospholipid peroxidation. Biochim Biophys Acta. 2012;1818: 2465-2475.
20. Gargalovic PS, Imura M, Zhang B, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Patel S, Nelson SF, Horvath S, Berliner JA, Kirchgessner TG, Lusis AJ. Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids. Proc Natl Acad Sci USA. 2006;103:12741-12746.
21. Romanoski CE, Che N, Yin F, Mai N, Pouldar D, Civelek M, Pan C, Lee S, Vakili L, Yang WP, Kayne P, Mungrue IN, Araujo JA, Berliner JA, Lusis AJ. Network for activation of human endothelial cells by oxidized phospholipids: A critical role of heme oxygenase 1. Circulation Research. 2011;109:e27-e41.
22. Afonyushkin T, Oskolkova OV, Philippova M, Resink TJ, Erne P, Binder BR, Bochkov VN. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler, Thromb, and Vasc Biol. 2010;30: 1007-1013.
23. Doyle B, Caplice N. Plaque neovascularization and antiangiogenic therapy for atherosclerosis. J Am Coll Cardiol. 2007;49:2073-2080.
24. Birukova AA, Lee S, Starosta V, Wu T, Ho T, Kim J, Berliner JA, Birukov KG. A role for VEGFR2 activation in endothelial responses caused by barrier disruptive oxpapc concentrations. PLoS One. 2012;7: e30957.
25. Starosta V, Wu T, Zimman A, Pham D, Tian X, Oskolkova O, Bochkov V, Berliner JA, Birukova AA, Birukov KG. Differential regulation of endothelial cell permeability by high and low doses of oxidized 1-palmitoyl-2-arachidonyl- sn-glycero-3-phosphocholine. Am J Respir Cell Mol Biol. 2012;46:331-341.
26. Gong KW, Zhao W, Li N, Barajas B, Kleinman M, Sioutas C, Horvath S, Lusis AJ, Nel A, Araujo JA. Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells. Genome Biol. 2007;8:R149.
27. Horkko S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder G, Berliner JA, Friedman P, Dennis EA, Curtiss LK, Palinski W, Witztum JL. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest. 1999;103:117-128.
28. Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Gugiu B, Fox PL, Hoff HF, Salomon RG, Hazen SL. 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.
29. Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Febbraio M, Hajjar DP, Silverstein RL, Hoff HF, Salomon RG, Hazen SL. 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.
30. Kadl A, Sharma PR, Chen W, Agrawal R, Meher AK, Rudraiah S, Grubbs N, Sharma R, Leitinger N. Oxidized phospholipid-induced inflammation is mediated by toll-like receptor 2. Free Radic Biol Med. 2011;51:1903-1909.
31. Silva AR, de Assis EF, Caiado LF, Marathe GK, Bozza MT, McIntyre TM, Zimmerman GA, Prescott SM, Bozza PT, Castro-Faria-Neto HC. 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.
32. Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M, Feric NT, Koschinsky ML, Harkewicz R, Witztum JL, Tsimikas S, Golenbock D, Moore KJ, Tabas I. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010;12:467-482.
33. Chang MK, Binder CJ, Miller YI, Subbanagounder G, Silverman GJ, Berliner JA, Witztum JL. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med. 2004;200: 1359-1370.
34. Kadl A, Meher AK, Sharma PR, Lee MY, Doran AC, Johnstone SR, Elliott MR, Gruber F, Han J, Chen W, Kensler T, Ravichandran KS, Isakson BE, Wamhoff BR, Leitinger N. Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via NRF2. Circulation Research. 2010;107:737-746.
35. Shamshiev AT, Ampenberger F, Ernst B, Rohrer L, Marsland BJ, Kopf M. Dyslipidemia inhibits toll-like receptor-induced activation of cd8alpha-negative dendritic cells and protective th1 type immunity. J Exp Med. 2007;204:441-452.
36. Bluml S, Zupkovitz G, Kirchberger S, Seyerl M, Bochkov VN, Stuhlmeier K, Majdic O, Zlabinger GJ, Seiser C, Stockl J. Epigenetic regulation of dendritic cell differentiation and function by oxidized phospholipids. Blood. 2009;114:5481-5489.
37. Cruz D, Watson AD, Miller CS, Montoya D, Ochoa MT, Sieling PA, Gutierrez MA, Navab M, Reddy ST, Witztum JL, Fogelman AM, Rea TH, Eisenberg D, Berliner J, Modlin RL. Host-derived oxidized phospholipids and hdl regulate innate immunity in human leprosy. J Clin Invest. 2008;118:2917-2928.
38. Pidkovka NA, Cherepanova OA, Yoshida T, Alexander MR, Deaton RA, Thomas JA, Leitinger N, Owens GK. Oxidized phospholipids induce phenotypic switching of vascular smooth muscle cells in vivo and in vitro. Circ Res. 2007;101:792-801.
39. Cherepanova OA, Pidkovka NA, Sarmento OF, Yoshida T, Gan Q, Adiguzel E, Bendeck MP, Berliner J, Leitinger N, Owens GK. Oxidized phospholipids induce type viii collagen expression and vascular smooth muscle cell migration. Circ Res. 2009;104:609-618.
40. Johnstone SR, Ross J, Rizzo MJ, Straub AC, Lampe PD, Leitinger N, Isakson BE. Oxidized phospholipid species promote in vivo differential cx43 phosphorylation and vascular smooth muscle cell proliferation. Am J Pathol. 2009;175:916-924.
41. Loidl A, Sevcsik E, Riesenhuber G, Deigner HP, Hermetter A. Oxidized phospholipids in minimally modified low density lipoprotein induce apoptotic signaling via activation of acid sphingomyelinase in arterial smooth muscle cells. J Biol Chem. 2003;278:32921-32928.
42. Chen R, Chen X, Salomon RG, McIntyre TM. Platelet activation by low concentrations of intact oxidized ldl particles involves the paf receptor. Arterioscler Thromb Vasc Biol. 2009;29:363-371.
43. Thomas CP, Morgan LT, Maskrey BH, Murphy RC, Kuhn H, Hazen SL, Goodall AH, Hamali HA, Collins PW, O'Donnell VB. Phospholipidesterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation. J Biol Chem. 2010;285:6891-6903.
44. Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. Hdl and cardiovascular disease: Atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8:222-232.
45. Bowry VW, Stanley KK, Stocker R. High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci USA. 1992;89:10316-10320.
46. Szapacs ME, Kim HY, Porter NA, Liebler DC. Identification of proteins adducted by lipid peroxidation products in plasma and modifications of apolipoprotein a1 with a novel biotinylated phospholipid probe. J Proteome Res. 2008;7:4237-4246.
47. Oskolkova OV, Afonyushkin T, Preinerstorfer B, Bicker W, von Schlieffen E, Hainzl E, Demyanets S, Schabbauer G, Lindner W, Tselepis AD, Wojta J, Binder BR, Bochkov VN. Oxidized phospholipids are more potent antagonists of lipopolysaccharide than inducers of inflammation. J Immunol. 2010;185:7706-7712.
48. Ashraf MZ, Kar NS, Chen X, Choi J, Salomon RG, Febbraio M, Podrez EA. Specific oxidized phospholipids inhibit scavenger receptor bi-mediated selective uptake of cholesteryl esters. J Biol Chem. 2008; 283:10408-10414.
49. West XZ, Malinin NL, Merkulova AA, Tischenko M, Kerr BA, Borden EC, Podrez EA, Salomon RG, Byzova TV. Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature. 2010;467:972-976.
50. Imai Y, Kuba K, Neely GG, et al. Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133:235-249.
51. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ. Cd36 ligands promote sterile inflammation through assembly of a toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11:155-161.
52. Walton KA, Hsieh X, Gharavi N, Wang S, Wang G, Yeh M, Cole AL, Berliner JA. Receptors involved in the oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3- phosphorylcholine-mediated synthesis of interleukin-8. A role for toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. J Biol Chem. 2003; 278:29661-29666.
53. Li R, Mouillesseaux KP, Montoya D, Cruz D, Gharavi N, Dun M, Koroniak L, Berliner JA. Identification of prostaglandin e2 receptor subtype 2 as a receptor activated by oxpapc. Circ Res. 2006;98: 642-650.
54. 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.
55. Smiley PL, Stremler KE, Prescott SM, Zimmerman GA, McIntyre TM. Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor. J Biol Chem. 1991;266:11104-11110.
56. Levitan I, Shentu TP. Impact of oxldl on cholesterol-rich membrane rafts. J Lipids. 2011;2011:730209.
57. Sabatini K, Mattila JP, Megli FM, Kinnunen PK. Characterization of two oxidatively modified phospholipids in mixed monolayers with dppc. Biophys J. 2006;90:4488-4499.
58. Yeh M, Cole AL, Choi J, et al. Role for sterol regulatory elementbinding protein in activation of endothelial cells by phospholipid oxidation products. Circ Res. 2004;95:780-788.
59. Greenberg ME, Li XM, Gugiu BG, Gu X, Qin J, Salomon RG, Hazen SL. The lipid whisker model of the structure of oxidized cell membranes. J Biol Chem. 2008;283:2385-2396.
60. Gao D, Ashraf MZ, Kar NS, Lin D, Sayre LM, Podrez EA. Structural basis for the recognition of oxidized phospholipids in oxidized low density lipoproteins by class b scavenger receptors CD36 and SR-BI. J Biol Chem. 2010;285:4447-4454.
61. Sun M, Finnemann SC, Febbraio M, Shan L, Annangudi SP, Podrez EA, Hoppe G, Darrow R, Organisciak DT, Salomon RG, Silverstein RL, Hazen SL. Light-induced oxidation of photoreceptor outer segment phospholipids generates ligands for CD36-mediated phagocytosis by retinal pigment epithelium: A potential mechanism for modulating outer segment phagocytosis under oxidant stress conditions. J Biol Chem. 2006;281:4222-4230.
62. Febbraio M, Guy E, Silverstein RL. Stem cell transplantation reveals that absence of macrophage CD36 is protective against atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:2333-2338.
63. Mullick AE, Soldau K, Kiosses WB, Bell TA III, Tobias PS, Curtiss LK. Increased endothelial expression of toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J Exp Med. 2008;205:373-383.
64. Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M. Lack of toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein e. Proc Natl Acad Sci USA. 2004;101:10679-10684.
65. Subbanagounder G, Leitinger N, Shih PT, Faull KF, Berliner JA. 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.
66. Gugiu BG, Mouillesseaux K, Duong V, Herzog T, Hekimian A, Koroniak L, Vondriska TM, Watson AD. Protein targets of oxidized phospholipids in endothelial cells. J Lipid Res. 2008;49:510-520.
67. Moumtzi A, Trenker M, Flicker K, Zenzmaier E, Saf R, Hermetter A. Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells. J Lipid Res. 2007;48:565-582.
68. Chen R, Brady E, McIntyre TM. Human tmem30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells. J Immunol. 2011;186:3215-3225.
69. Stemmer U, Hermetter A. Protein modification by aldehydophospholipids and its functional consequences. Biochim Biophys Acta. 2012;in press.
70. Kincer JF, Uittenbogaard A, Dressman J, Guerin TM, Febbraio M, Guo L, Smart EJ. Hypercholesterolemia promotes a cd36-dependent and endothelial nitric-oxide synthase-mediated vascular dysfunction. J Biol Chem. 2002;277:23525-23533.
71. Rahaman SO, Zhou G, Silverstein RL. Vav protein guanine nucleotide exchange factor regulates cd36 protein-mediated macrophage foam cell formation via calcium and dynamin-dependent processes. J Biol Chem. 2011;286:36011-36019.
72. Venkatesha RT, Ahamed J, Nuesch C, Zaidi AK, Ali H. Plateletactivating factor-induced chemokine gene expression requires nf-kappab activation and ca2/calcineurin signaling pathways: inhibition by receptor phosphorylation and beta-arrestin recruitment. J Biol Chem. 2004;279:44606-44612.
73. Imaizumi S, Grijalva V, Priceman S, Wu L, Su F, Farias-Eisner R, Hama S, Navab M, Fogelman AM, Reddy ST. Mitogen-activated protein kinase phosphatase-1 deficiency decreases atherosclerosis in apolipoprotein e null mice by reducing monocyte chemoattractant protein-1 levels. Mol Genet Metab. 2010;101:66-75.
74. Yvan-Charvet L, Pagler TA, Seimon TA, Thorp E, Welch CL, Witztum JL, Tabas I, Tall AR. Abca1 and abcg1 protect against oxidative stressinduced macrophage apoptosis during efferocytosis. Circ Res. 2010;106: 1861-1869.
75. Chen R, Yang L, McIntyre TM. Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. J Biol Chem. 2007;282:24842-24850.
76. Kagan VE, Gleiss B, Tyurina YY, Tyurin VA, Elenstrom-Magnusson C, Liu SX, Serinkan FB, Arroyo A, Chandra J, Orrenius S, Fadeel B. 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.
77. Chen K, Li W, Major J, Rahaman SO, Febbraio M, Silverstein RL. Vav guanine nucleotide exchange factors link hyperlipidemia and a prothrombotic state. Blood. 2011;117:5744-5750.
78. Ishii H, Tezuka T, Ishikawa H, Takada K, Oida K, Horie S. Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of rarbeta-rxralpha heterodimers and sp1 and sp3 to their binding sequences in the tm promoter. Blood. 2003;101:4765-4774.
79. Bochkov VN, Mechtcheriakova D, Lucerna M, Huber J, Malli R, Graier WF, Hofer E, Binder BR, Leitinger N. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of erk/egr-1 and ca(-)/nfat. Blood. 2002;99:199-206.
80. Zimman A, Mouillesseaux KP, Le T, Gharavi NM, Ryvkin A, Graeber TG, Chen TT, Watson AD, Berliner JA. Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2007;27: 332-338.
81. Ohkura N, Hiraishi S, Itabe H, Hamuro T, Kamikubo Y, Takano T, Matsuda J, Horie S. Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of tissue factor pathway inhibitor through association with its carboxy-terminal region. Antioxid Redox Signal. 2004;6:705-712.
82. O'Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin CD, et al. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques: implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest. 1993;92:945-951.
83. Huo Y, Hafezi-Moghadam A, Ley K. Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions. Circ Res. 2000;87: 153-159.
84. Cole AL, Subbanagounder G, Mukhopadhyay S, Berliner JA, Vora DK. Oxidized phospholipid-induced endothelial cell/monocyte interaction is mediated by a camp-dependent r-ras/pi3-kinase pathway. Arterioscler Thromb Vasc Biol. 2003;23:1384-1390.
85. Birukova AA, Zebda N, Fu P, Poroyko V, Cokic I, Birukov KG. Association between adherens junctions and tight junctions via rap1 promotes barrier protective effects of oxidized phospholipids. J Cell Physiol. 2010;226:2052-2062.
86. Birukova AA, Zebda N, Cokic I, Fu P, Wu T, Dubrovskyi O, Birukov KG. P190rhogap mediates protective effects of oxidized phospholipids in the models of ventilator-induced lung injury. Exp Cell Res. 2011;317: 859-872.
87. van Nieuw Amerongen GP, Koolwijk P, Versteilen A, van Hinsbergh VW. Involvement of rhoa/rho kinase signaling in vegf-induced endothelial cell migration and angiogenesis in vitro. Arterioscler Thromb Vasc Biol. 2003;23:211-217.
88. DeMaio L, Rouhanizadeh M, Reddy S, Sevanian A, Hwang J, Hsiai TK. Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2006;290:H674-H683.
89. Zimman A, Chen SS, Komisopoulou E, Titz B, Martinez-Pinna R, Kafi A, Berliner JA, Graeber TG. Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis. J Proteome Res. 2010;9:2812-2824.
90. Nonas S, Miller I, Kawkitinarong K, Chatchavalvanich S, Gorshkova I, Bochkov VN, Leitinger N, Natarajan V, Garcia JG, Birukov KG. Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med. 2006;173: 1130-1138.
91. Li R, Chen W, Yanes R, Lee S, Berliner JA. Okl38 is an oxidative stress response gene stimulated by oxidized phospholipids. J Lipid Res. 2007; 48:709-715.
92. Jyrkkanen HK, Kansanen E, Inkala M, et al. Nrf2 regulates antioxidant gene expression evoked by oxidized phospholipids in endothelial cells and murine arteries in vivo. Circ Res. 2008;103:e1-e9.
93. Afonyushkin T, Oskolkova OV, Binder BR, Bochkov VN. Involvement of ck2 in activation of electrophilic genes in endothelial cells by oxidized phospholipids. J Lipid Res. 2010;52:98-103.
94. Lee S, Li R, Kim B, Palvolgyi R, Ho T, Yang QZ, Xu J, Szeto WL, Honda H, Berliner JA. Ox-papc activation of pmet system increases expression of heme oxygenase-1 in human aortic endothelial cell. J Lipid Res. 2009;50:265-274.
95. Kronke G, Bochkov VN, Huber J, Gruber F, Bluml S, Furnkranz A, Kadl A, Binder BR, Leitinger N. Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of campresponsive element-binding protein. J Biol Chem. 2003;278: 51006-51014.
96. Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Baruch-Oren T, Berliner JA, Kirchgessner TG, Lusis AJ. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26: 2490-2496.
97. Lee S, Gharavi NM, Honda H, Chang I, Kim B, Jen N, Li R, Zimman A, Berliner JA. A role for nadph oxidase 4 in the activation of vascular endothelial cells by oxidized phospholipids. Free Radic Biol Med. 2009; 47:145-151.
98. Vladykovskaya E, Sithu SD, Haberzettl P, et al. The lipid peroxidation product, 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J Biol Chem. 2012;287: 11398-11409.
99. Romanoski CE, Lee S, Kim MJ, Ingram-Drake L, Plaisier CL, Yordanova R, Tilford C, Guan B, He A, Gargalovic PS, Kirchgessner TG, Berliner JA, Lusis AJ. Systems genetics analysis of gene-byenvironment interactions in human cells. Am J Hum Genet. 2010;86: 399-410.
100. Gharavi NM, Baker NA, Mouillesseaux KP, Yeung W, Honda HM, Hsieh X, Yeh M, Smart EJ, Berliner JA. Role of endothelial nitric oxide synthase in the regulation of srebp activation by oxidized phospholipids. Circ Res. 2006;98:768-776.
101. Colgan SM, Hashimi AA, Austin RC. Endoplasmic reticulum stress and lipid dysregulation. Expert Rev Mol Med. 2011;13:e4.
102. Singh NK, Wang D, Kundumani-Sridharan V, Van Quyen D, Niu J, Rao GN. 15-lipoxygenase-1-enhanced src-janus kinase 2-signal transducer and activator of transcription 3 stimulation and monocyte chemoattractant protein-1 expression require redox-sensitive activation of epidermal growth factor receptor in vascular wall remodeling. J Biol Chem. 2011;286:22478-22488.
103. Gharavi NM, Alva JA, Mouillesseaux KP, Lai C, Yeh M, Yeung W, Johnson J, Szeto WL, Hong L, Fishbein M, Wei L, Pfeffer LM, Berliner JA. Role of the jak/stat pathway in the regulation of interleukin-8 transcription by oxidized phospholipids in vitro and in atherosclerosis in vivo. J Biol Chem. 2007;282:31460-31468.
104. Springstead JR, Gugiu BG, Lee S, Cha S, Watson AD, Berliner JA. Evidence for the importance of oxpapc interaction with cysteines in regulating endothelial cell function. J Lipid Res. 2012;53:1304-1315.
105. Lee H, Shi W, Tontonoz P, Wang S, Subbanagounder G, Hedrick CC, Hama S, Borromeo C, Evans RM, Berliner JA, Nagy L. 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.
106. Subbanagounder G, Wong JW, Lee H, Faull KF, Miller E, Witztum JL, Berliner JA. 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.
107. Tan W, Palmby TR, Gavard J, Amornphimoltham P, Zheng Y, Gutkind JS. An essential role for rac1 in endothelial cell function and vascular development. FASEB J. 2008;22:1829-1838.
108. Yoshida T, Gan Q, Owens GK. Kruppel-like factor 4, elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am J Physiol Cell Physiol. 2008;295:C1175-C1182.
109. Chatterjee S, Berliner JA, Subbanagounder GG, Bhunia AK, Koh S. Identification of a biologically active component in minimally oxidized low density lipoprotein (mm-ldl) responsible for aortic smooth muscle cell proliferation. Glycoconj J. 2004;20:331-338.
110. Johnstone SR, Kroncke BM, Straub AC, Best AK, Dunn CA, Mitchell LA, Peskova Y, Nakamoto RK, Koval M, Lo CW, Lampe PD, Columbus L, Isakson BE. Mapk phosphorylation of connexin 43 promotes binding of cyclin e and smooth muscle cell proliferation. Circ Res. 2012;111:201-211.
111. Poeckel D, Zemski Berry KA, Murphy RC, Funk CD. Dual 12/15-and 5-lipoxygenase deficiency in macrophages alters arachidonic acid metabolism and attenuates peritonitis and atherosclerosis in apoe knock-out mice. J Biol Chem. 2009;284:21077-21089.
112. McMillen TS, Heinecke JW, LeBoeuf RC. Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation. 2005;111:2798-2804.
113. Subbanagounder G, Leitinger N, Schwenke DC, Wong JW, Lee H, Rizza C, Watson AD, Faull KF, Fogelman AM, Berliner JA. Determinants of bioactivity of oxidized phospholipids: specific oxidized fatty acyl groups at the sn-2 position. Arterioscler Thromb Vasc Biol. 2000; 20:2248-2254.
114. Liu J, Chen R, Marathe GK, Febbraio M, Zou W, McIntyre TM. Circulating platelet-activating factor is primarily cleared by transport, not intravascular hydrolysis by lipoprotein-associated phospholipase a2/paf acetylhydrolase. Circ Res. 2011;108:469-477.
115. Mallat Z, Lambeau G, Tedgui A. Lipoprotein-associated and secreted phospholipases a in cardiovascular disease: Roles as biological effectors and biomarkers. Circulation. 2010;122:2183-2200.
116. Spite M, Baba SP, Ahmed Y, Barski OA, Nijhawan K, Petrash JM, Bhatnagar A, Srivastava S. Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes. Biochem J. 2007; 405:95-105.
117. Chen JW, Dodia C, Feinstein SI, Jain MK, Fisher AB. 1-cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase a2 activities. J Biol Chem. 2000;275:28421-28427.
118. Toppo S, Flohe L, Ursini F, Vanin S, Maiorino M. Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. Biochim Biophys Acta. 2009;1790:1486-1500.
119. Guo Z, Ran Q, Roberts LJ II, Zhou L, Richardson A, Sharan C, Wu D, Yang H. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein e-deficient mice. Free Radic Biol Med. 2008;44:343-352.
120. Vladykovskaya E, Ozhegov E, Hoetker JD, Xie Z, Ahmed Y, Suttles J, Srivastava S, Bhatnagar A, Barski OA. Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. J Lipid Res. 2011;52:2209-2225.
121. Srivastava S, Vladykovskaya E, Barski OA, Spite M, Kaiserova K, Petrash JM, Chung SS, Hunt G, Dawn B, Bhatnagar A. Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein e-null mice. Circ Res. 2009;105:793-802.
122. Tsimikas S, Miyanohara A, Hartvigsen K, Merki E, Shaw PX, Chou MY, Pattison J, Torzewski M, Sollors J, Friedmann T, Lai NC, Hammond HK, Getz GS, Reardon CA, Li AC, Banka CL, Witztum JL. Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression. J Am Coll Cardiol. 2011;58:1715-1727.
123. Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witztum JL, Palinski W, Schwenke D, Salomon RG, Sha W, Subbanagounder G, Fogelman AM, Berliner JA. 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.
124. Subbanagounder G, Deng Y, Borromeo C, Dooley AN, Berliner JA, Salomon RG. Hydroxy alkenal phospholipids regulate inflammatory functions of endothelial cells. Vasc Pharm. 2002;38:201-209.
125. Deng YH, Salomon RG. Total synthesis of gamma-hydroxy-alpha, betaunsaturated aldehydic esters of cholesterol and 2-lysophosphatidylcholine. J Org Chem. 1998;63:7789-7794.
126. Choi J, Laird JM, Salomon RG. An efficient synthesis of gamma-hydroxyalpha, beta-unsaturated aldehydic esters of 2- lysophosphatidylcholine. Bioorg Med Chem. 2011;19:580-587.
127. Gao S, Zhang R, Greenberg ME, Sun M, Chen X, Levison BS, Salomon RG, Hazen SL. Phospholipid hydroxyalkenals, a subset of recently discovered endogenous cd36 ligands, spontaneously generate novel furan-containing phospholipids lacking cd36 binding activity in vivo. J Biol Chem. 2006;281:31298-31308.
128. Sun M, Deng Y, Batyreva E, Sha W, Salomon RG. Novel bioactive phospholipids: Practical total syntheses of products from the oxidation of arachidonic and linoleic esters of 2-lysophosphatidylcholine(1). J Org Chem. 2002;67:3575-3584.
129. Legrand AB, Wang J, Sobo G, Blair IA, Brash AR, Oates JA. Incorporation of 12(s)-hydroxyeicosatetraenoic acid into the phosphatidylcholine signaling pathway. Biochimica et Biophysica Acta. 1996;1301: 150-160.
130. Zhang JY, Nobes BJ, Wang JM, Blair IA. Characterization of hydroxyeicosatetraenoic acids and hydroxyeicosatetraenoic acid phosphatidylcholines by liquid secondary-ion tandem mass-spectrometry. Biol Mass Spectrom. 1994;23:399-405.
131. Cho YH, Ziboh VA. Incorporation of 13-hydroxyoctadecadienoic acid
132. Sun M, Salomon RG. Oxidative fragmentation of hydroxy octadecadienoates generates biologically active gamma-hydroxyalkenals. JACS. 2004;126:5699-5708.
133. Watson AD, Subbanagounder G, Welsbie DS, Faull KF, Navab M, Jung ME, Fogelman AM, Berliner JA. Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. J Biol Chem. 1999;274:24787-24798.
134. Jung ME, Berliner JA, Koroniak L, Gugiu BG, Watson AD. Improved synthesis of the epoxy isoprostane phospholipid peipc and its reactivity with amines. Org Lett. 2008;10:4207-4209.
135. Jung ME, Berliner JA, Angst D, Yue D, Koroniak L, Watson AD, Li R. Total synthesis of the epoxy isoprostane phospholipids peipc and pecpc. Org Lett. 2005;7:3933-3935.
136. Salomon RG, Subbanagounder G, Singh U, O'Neil J, Hoff HF. Oxidation of low-density lipoproteins produces levuglandin-protein adducts. Chem Res Toxicol. 1997;10:750-759.
137. Brose SA, Thuen BT, Golovko MY. Lc/ms/ms method for analysis of e-2 series prostaglandins and isoprostanes. J Lipid Res. 2011;52: 850-859.
138. Milne GL, Porter NA. Separation and identification of phospholipid peroxidation products. Lipids. 2001;36:1265-1275.