Role of lipoprotein-associated phospholipase A2 in atherosclerosis: Biology, epidemiology, and possible therapeutic target

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 25, Issue 5, 2005, Pages 923-931

  Zalewski, Andrew ^a,b   Macphee, Colin ^a  

^a GLAXOSMITHKLINE   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Atherosclerosis; Inflammation; Lipoprotein associated phospholipase A 2

Indexed keywords

ANTILIPEMIC AGENT; ANTITHROMBOCYTIC AGENT; ATORVASTATIN; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; FATTY ACID; LIPID; LIPOPROTEIN; LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2; LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 INHIBITOR; LOW DENSITY LIPOPROTEIN; LYSOPHOSPHATIDYLCHOLINE; PHOSPHOLIPASE A2; PHOSPHOLIPID; PHOSPHOLIPID DERIVATIVE; PRAVASTATIN; PROTEIN INHIBITOR; THROMBOCYTE ACTIVATING FACTOR; UNCLASSIFIED DRUG;

ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CONTROLLED STUDY; GENE; HIGH RISK PATIENT; HUMAN; HYDROLYSIS; INFLAMMATION; INFLAMMATORY CELL; MEDICAL GENETICS; NONHUMAN; OXIDATION; PLA2G7 GENE; PREDICTION; PRIORITY JOURNAL; PROTEIN DEGRADATION; SHORT SURVEY;

ANIMALS; ATHEROSCLEROSIS; BLOOD VESSELS; ENZYME INHIBITORS; HUMANS; PHOSPHOLIPASES A; RISK FACTORS; VASCULITIS;

EID: 18244373708     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.ATV.0000160551.21962.a7     Document Type: Short Survey

References (96)

1. Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, Ellis SG, Lincoff AM, Topol EJ. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290:898-904.
2. Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB, Wilson PW. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA. 2003;290:891-897.
3. Qureshi AI, Suri MF, Kirmani JF, Divani AA. The relative impact of inadequate primary and secondary prevention on cardiovascular mortality in the United States. Stroke. 2004;35:2346-2350.
4. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.
5. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364: 685-696.
6. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-1143.
7. Balk EM, Lau J, Goudas LC, Jordan HS, Kupelnick B, Kim LU, Karas RH. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med. 2003;139: 670-682.
8. O'Keefe JH, Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004;43:2142-2146.
9. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Beider R, Joyal SV, Hill KA, Pfeffer MA, Skene AM. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504.
10. Mertens A, Holvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J. 2001;15:2073-2084.
11. Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H, Shinno K, Nagahiro S. Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol. 2002;22:1649-1654.
12. Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Takano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation. 2001;103:1955-1960.
13. Tsimikas S, Bergmark C, Beyer RW, Patel R, Pattison J, Miller E, Juliano J, Witztum JL. 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.
14. Penny WF, Ben Yehuda O, Kuroe K, Long J, Bond A, Bhargava V, Peterson JF, McDaniel M, Juliano J, Witztum JL, Ross J, Jr., Peterson KL. Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein. J Am Coll Cardiol. 2001; 37:766-774.
15. Subbanagounder G, Leitinger N, Schwenke D, 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.
16. Subbanagounder G, Wong JW, Lee H, Faull KF, Miller E, Witzum JL, Berliner JA. Epoxyisoprostane and epoxycyclopentenone phospholipids regulate monocyte chemotactic protein-1 and interleukin-8 synthesis. J Biol Chem. 2002;277:7271-7281.
17. Steinberg D. Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med. 2002;8:1211-1217.
18. Subbanagounder G, Watson AD, Berliner JA. Bioactive products of phospholipid oxidation: isolation, identification, measurement and activity. Free Rad Biol Med. 2000;28:1751-1761.
19. Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witzum JL, Palinsky W, Schwenke D, Salomon RG, Sha W, Subbanagrounder G, Fogelman AM, Berliner JA. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoproteins that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem. 1997;272:13597-13603.
20. Hara A, Taketomi T. Characterization and change in phospholipids in the aorta of Watanabe heritable hyperlipidemic rabbit. Jpn J Exp Med. 1990; 60:311-318.
21. Six DA, Dennis EA. The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochim Biophys Acta. 2000;1488:1-19.
22. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 1995;374:549-553.
23. Stafforini DM, Prescott SM, McIntyre TM. Human plasma platelet-activating factor acetylhydrolase. Purification and properties. J Biol Chem. 1987;262:4223-4230.
24. Min JH, Jain MK, Wilder C, Paul L, Apitz-Castro R, Aspleaf DC, Gelb MH. Membrane-bound plasma platelet activating factor acetylhydrolase acts on substrate in the aqueous phase. Biochemistry. 1999;38: 12935-12942.
25. Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM. Platelet-activating factor acetylhydrolases. J Biol Chem. 1997;272:17895-17898.
26. Watson AD, Navab M, Hama SY, Sevanian A, Prescott SM, Stafforini DM, McIntyre TM, Du BN, Fogelman AM, Berliner JA. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest. 1995;95:774-782.
27. Birukov KG, Bochkov VN, Birukova AA, Kawkitinarong K, Rios A, Leitner A, Verin AD, Bokoch GM, Leitinger N, Garcia JG. Epoxycyclopentenone-containing oxidized phospholipids restore endothelial barrier function via Cdc42 and Rac. Circ Res. 2004;95:892-901.
28. Bochkov VN, Leitinger N. Anti-inflammatory properties of lipid oxidation products. J Mol Med. 2003;81:613-626.
29. Henig NR, Aitken ML, Liu MC, Yu AS, Henderson WR, Jr. Effect of recombinant human platelet-activating factor-acetylhydrolase on allergen-induced asthmatic responses. Am J Respir Crit Care Med. 2000; 162:523-527.
30. Opal S, Laterre PF, Abraham E, Francois B, Wittebole X, Lowry S, Dhainaut JF, Warren B, Dugernier T, Lopez A, Sanchez M, Demeyer I, Jauregui L, Lorente JA, McGee W, Reinhart K, Kljucar S, Souza S, Pribble J. Recombinant human platelet-activating factor acetylhydrolase for treatment of severe sepsis: results of a phase III, multicenter, randomized, double-blind, placebo-controlled, clinical trial. Crit Care Med. 2004;32:332-341.
31. Rodrigo L, Mackness B, Durrington PN, Hernandez A, Mackness MI. Hydrolysis of platelet-activating factor by human serum paraoxonase. Biochem J. 2001;354:1-7.
32. Subramanian VS, Goyal J, Miwa M, Sugatami J, Akiyama M, Liu M, Subbaiah PV. Role of lecithin-cholesterol acyltransferase in the metabolism of oxidized phospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma. Biochim Biophys Acta. 1999; 1439:95-109.
33. Marathe GK, Zimmerman GA, McIntyre TM. Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. J Biol Chem. 2003;278: 3937-3947.
34. Kume N, Cybulsky MI, Gimbrone MA, Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992;90:1138-1144.
35. Zhu Y, Lin JH, Liao HL, Verna L, Stemerman MB. Activation of ICAM-1 promoter by lysophosphatidylcholine: possible involvement of protein tyrosine kinases. Biochim Biophys Acta. 1997;1345:93-98.
36. Takahara N, Kashiwagi A, Maegawa H, Shigeta Y. Lysophosphatidyl-choline stimulates the expression and production of MCP-1 by human vascular endothelial cells. Metabolism. 1996;45:559-564.
37. Wong JT, Tran K, Pierce GN, Chan AC, O K, Choy PC. Lysophosphatidylcholine stimulates the release of arachidonic acid in human endothelial cells. J Biol Chem. 1998;273:6830-6836.
38. Rikitake Y, Kawashima S, Yamashita T, Ueyama T, Ishido S, Hotta H, Hirata K, Yokoyama M. Lysophosphatidylcholine inhibits endothelial cell migration and proliferation via inhibition of the extracellular signal-regulated kinase pathway. Arterioscler Thromb Vasc Biol. 2000;20: 1006-1012.
39. Fukao M, Hattori Y, Kanno M, Sakuma I, Kitabatake A. Structural differences in the ability of lysophospholipids to inhibit endothelium-dependent hyperpolarization by acetylcholine in rat mesenteric arteries. Biochem Biophys Res Commun. 1996;227:479-483.
40. Chen L, Liang B, Froese DE, Liu S, Wong JT, Tran K, Hatch GM, Mymin D, Kroeger EA, Man RY, Choy PC. Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophosphatidylcholine composition on vascular relaxation. J Lipid Res. 1997;38:546-553.
41. Takahashi M, Okazaki H, Ogata Y, Takeuchi K, Ikeda U, Shimada K. Lysophosphatidylcholine induces apoptosis in human endothelial cells through a p38-mitogen-activated protein kinase-dependent mechanism. Atherosclerosis. 2002;161:387-394.
42. Rong JX, Berman JW, Taubman MB, Fisher EA. Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002; 22:1617-1623.
43. Yamakawa T, Tanaka S, Yamakawa Y, Kamei J, Numaguchi K, Motley ED, Inagami T, Eguchi S. Lysophosphatidylcholine activates extra-cellular signal-regulated kinases 1/2 through reactive oxygen species in rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002; 22:752-758.
44. Chai YC, Howe PH, DiCorleto PE, Chisolm GM. Oxidized low density lipoprotein and lysophosphatidylcholine stimulate cell cycle entry in vascular smooth muscle cells. Evidence for release of fibroblast growth factor-2. J Biol Chem. 1996;271:17791-17797.
45. Kohno M, Yokokawa K, Yasunari K, Minami M, Kano H, Hanehira T, Yoshikawa J. Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration. Circulation. 1998;98:353-359.
46. Chang MY, Tsoi C, Wight TN, Chait A. Lysophosphatidylcholine regulates synthesis of biglycan and the proteoglycan form of macrophage colony stimulating factor. Arterioscler Thromb Vasc Biol. 2003;23: 809-815.
47. Hsieh CC, Yen MH, Liu HW, Lau YT. Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular smooth muscle cells: in comparison with oxidized LDL. Atherosclerosis. 2000;151:481-491.
48. Liu-Wu Y, Hurt-Camejo E, Wiklund O. Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. Atherosclerosis. 1998; 137:351-357.
49. Oestvang J, Anthonsen MW, Johansen B. Role of secretory and cytosolic phospholipase A(2) enzymes in lysophosphatidykholine-stimulated monocyte arachidonic acid release. FEBS Lett. 2003;555:257-262.
50. Carpenter KL, Dennis IF, Challis IR, Osborn DP, Macphee CH, Leake DS, Arends MJ, Mitchinson MJ. Inhibition of lipoprotein-associated phospholipase A2 diminishes the death-inducing effects of oxidised LDL on human monocyte-macrophages. FEBS Lett. 2001;505:357-363.
51. McMurray HF, Parthasarathy S, Steinberg D. Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J Clin Invest. 1993;92:1004-1008.
52. Macphee CH, Moores KE, Boyd HF, Dhanak D, Ife RJ, Leach CA, Leake DS, Milliner KJ, Patterson RA, Suckling KE, Tew DG, Hickey DM. Lipoprotein- associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. Biochem J. 1999;338(Pt 2):479-487.
53. Macphee CH. Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target. Curr Opin Pharmacol. 2001;1:121-125.
54. Kabarowski JH, Zhu K, Le LQ, Witte ON, Xu Y. Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Science. 2001;293:702-705.
55. Rikitake Y, Hirata K, Yamashita T, Iwai K, Kobayashi S, Itoh H, Ozaki M, Ejiri J, Shiomi M, Inoue N, Kawashima S, Yokoyama M. Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2002;22:2049-2053.
56. Stafforini DM, Satoh K, Atkinson DL, Tjoelker LW, Eberhardt C, Yoshida H, Imaizumi T, Takamatsu S, Zimmerman GA, McIntyre TM, Gray PW, Prescott SM. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest. 1996;97:2784-2791.
57. 2) deficiency patients. J Hum Genet. 2004;49:302-307.
58. Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K. A mutation in plasma platelet-activating factor acetylhydrolase (Val279->Phe) is a genetic risk factor for stroke. Stroke. 1997;28:2417-2420.
59. Yamada Y, Ichihara S, Fujimura T, Yokota M. Identification of the G994-> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men. Metabolism. 1998;47:177-181.
60. Unno N, Nakamura T, Kaneko H, Uchiyama T, Yamamoto N, Sugatani J, Miwa M, Nakamura S. Plasma platelet-activating factor acetylhydrolase deficiency is associated with atherosclerotic occlusive disease in japan. J Vasc Surg. 2000;32:263-267.
61. Unno N, Nakamura T, Mitsuoka H, Uchiyama T, Yamamoto N, Saito T, Sugatani J, Miwa M, Nakamura S. Association of a G994->T missense mutation in the plasma platelet-activating factor acetylhydrolase gene with risk of abdominal aortic aneurysm in Japanese. Ann Surg. 2002;235: 297-302.
62. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002; 347:1916-1923.
63. Kim PS, Arvan P. Endocrinopathies in the family of endoplasmic reticulum (ER) storage diseases: disorders of protein trafficking and the role of ER molecular chaperones. Endocr Rev. 1998;19:173-202.
64. Zhang K, Kaufman RJ. Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem. 2004;279:25935-25938.
65. Kruse S, Mao XQ, Heinzmann A, Blattmann S, Roberts MH, Braun S, Gao PS, Forster J, Kuehr J, Hopkin JM, Shirakawa T, Deichmann KA. The Ile 198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma. Am J Hum Genet. 2000;66:1522-1530.
66. Abuzeid AM, Hawe E, Humphries SE, Talmud PJ. Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. Atherosclerosis. 2003;168:283-288.
67. Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet. 2004;363: 689-695.
68. Walter MF, Jacob RF, Jeffers B, Ghadanfar MM, Preston GM, Buch J, Mason RP. Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study. J Am Coll Cardial. 2004; 44:1996-2002.
69. Packard CJ, O'Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GD. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000;343:1148-1155.
70. Blake GJ, Dada N, Fox JC, Manson JE, Ridker PM. A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women. J Am Coll Cardiol. 2001;38:1302-1306.
71. Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, Sharrett AR. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004;109:837-842.
72. Ballantyne C, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Sharrett AR, Wu KK, Myerson M, Chambless LE, Boerwinkle E. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities Study. Circulation. 2004;110:111-641. Abstract.
73. Koenig W, Khuseyinova N, Lowel H, Trischler G, Meisinger C. Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany. Circulation. 2004; 110:1903-1908.
74. Oei H-HS, van der Meer I, Hofman A, Koudstaal P, Breteler M, Witteman J. Lipoprotein-associated phospholipase A2 is associated with risk of coronary heart disease and stroke: The Rotterdam Study. Circulation. 2005;111:570-575.
75. Manolio T. Novel risk markers and clinical practice. N Engl J Med. 2003;349:1587-1589.
76. Asano K, Okamoto S, Fukunaga K, Shiomi T, Mori T, Iwata M, Ikeda Y, Yamaguchi K. Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma. Biochem Biophys Res Commun. 1999;261: 511-514.
77. Stafforini DM, Tjoelker LW, McCormick SP, Vaitkus D, McIntyre TM, Gray PW, Young SG, Prescott SM. Molecular basis of the interaction between plasma platelet-activating factor acetylhydrolase and low density lipoprotein. J Biol Chem. 1999;274:7018-7024.
78. Tselepis AD, Karabina SA, Stengel D, Piedagnel R, Chapman MJ, Ninio E. N-linked glycosylation of macrophage-derived PAF-AH is a major determinant of enzyme association with plasma HDL. J Lipid Res. 2001; 42:1645-1654.
79. Tselepis AD, Dentan C, Karabina SA, Chapman MJ, Ninio E. PAF-degrading acetylhydrolase is preferentially associated with dense LDL and VHDL-I in human plasma. Catalytic characteristics and relation to the monocyte-derived enzyme. Arterioscler Thromb Vasc Biol. 1995;15: 1764-1773.
80. Benitez S, Sanchez-Quesada JL, Ribas V, Jorba O, Blanco-Vaca F, Gonzalez-Sastre F, Ordonez-Llanos J. Platelet-activating factor acetylhydrolase is mainly associated with electronegative low-density lipoprotein subfraction. Circulation. 2003;108;92-96.
81. Sevanian A, Bittolo-Bon G, Cazzolato G, Hodis H, Hwang J, Zamburlini A, Maiorino M, Ursini F. LDL- is a lipid hydroperoxide-enriched circulating lipoprotein. J Lipid Res. 1997;38:419-428.
82. Sanchez-Quesada JL, Camacho M, Anton R, Benitez S, Vila L, Ordonez-Llanos J. Electronegative LDL of FH subjects: chemical characterization and induction of chemokine release from human endothelial cells. Atherosclerosis. 2003;166:261-270.
83. Yang CY, Raya JL, Chen HH, Chen CH, Abe Y, Pownall HJ, Taylor AA, Smith CV. Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteine. Arterioscler Thromb Vasc Biol. 2003;23:1083-1090.
84. Theilmeier G, De Geest B, Van Veldhoven PP, Stengel D, Michiels C, Lox M, Landeloos M, Chapman MJ, Ninio E, Collen D, Himpens B, Holvoet P. HDL-associated PAF-AH reduces endothelial adhesiveness in apoE-/- mice. FASEB J. 2000;14:2032-2039.
85. Quarck R, De Geest B, Stengel D, Mertens A, Lox M, Theilmeier G, Michiels C, Raes M, Bull H, Collen D, Van Veldhoven P, Ninio E, Holvoet P. Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2001;103:2495-2500.
86. Mertens A, Verhamme P, Bielicki JK, Philips MC, Quarck R, Verreth W, Stengel D, Ninio E, Navab M, Mackness B, Mackness M, Holvoet P. Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice. Circulation. 2003;107:1640-1646.
87. Singh U, Zhong S, Xiong M, Li T, Sniderman A, Teng BB. Increased plasma non-esterified fatty acids nad platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice. Clin Sci. 2004;106:421-432.
88. Hakkinen T, Luoma JS, Hiltunen MO, Macphee CH, Milliner KJ, Patel L, Rice SQ, Tew DG, Karkola K, Yla-Herttuala S. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 1999;19:2909-2917.
89. Kolodgie F, Burke A, Taye A, Liu W, Sudhir K, Virmani R. Lipoprotein-associated phospholipase A2 is highly expressed in macrophages of coronary lesions prone to rupture. Circulation. 2004;110:111-246. Abstract.
90. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000; 20:1262-1275.
91. Memon RA, Fuller J, Moser AH, Feingold KR, Grunfeld C. In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response. Am J Physiol. 1999;277:R94-R103.
92. Wu X, Zimmerman GA, Prescott SM, Stafforini DM. The p38 MAPK pathway mediates transcriptional activation of the plasma platelet-activating factor acetylhydrolase gene in macrophages stimulated with lipopolysaccharide. J Biol Chem. 2004;279:36158-36165.
93. Tsimihodimos V, Karabina SA, Tambaki AP, Bairaktari E, Goudevenos JA, Chapman MJ, Elisaf M, Tselepis AD. Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB. Arterioscler Thromb Vasc Biol. 2002;22:306-311.
94. Tsimihodimos V, Kakafika A, Tambaki AP, Bairaktari E, Chapman MJ, Elisaf M, Tselepis AD. Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins. J Lipid Res. 2003;44:927-934.
95. Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, Szarek M, Olsson AG, Schwartz GG. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial. Circulation. 2004;110:1406-1412.
96. 2) activity, an emerging CV risk marker, can be inhibited in atherosclerotic lesions and plasma by novel pharmacologic intervention: The results of a multicenter clinical study. Circulation. 2004;110:111-590. Abstract.