Skip to main content
SpringerLink
Log in

The role of phospholipases in lipid modification and atherosclerosis

  • Original Research
  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Phospholipases have received wide attention as it has become clear that several isoforms of the phospholipase family play a role in onset and progression of atherosclerosis. The release of free fatty acids (FFA) and lysophospholipids (lysoPL) provide metabolites for various inflammatory pathways, and this has been considered the main mechanism of phospholipase-driven inflammation. However, generation of FFA and lysoPL are only part of the story. The induction of low-density phospholipoprotein (LDL) aggregation and accumulation, receptor binding, co-regulation with cyclooxygenase (COX) and lipoxygenase (LO) pathways, internalization through heparan sulfate proteoglycan (HSPG) shuttling, and crosstalk between phospholipases all play a role in atherosclerosis.

Group IIA phospholipase has long been considered a key enzyme in the initiation of various inflammatory diseases, but new data also indicate a role in the subsequent resolution of inflammatory processes. Recently, secreted group V and group X phospholipase and platelet activating factora cetylhydrolase (PAF-AH) are also recognized as important enzymes in atherosclerosis, modifying LDL and leading to lipid accumulation.

The phospholipases and their function in atherosclerosis are not fully under-stood. Future investigations can deliver better insight in the complex role of these enzymes. The present review summarizes the current state of phospholipase research related to atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Williams, K.J. and Tabas, I. (1995). The response-to-retention hypothesis of early atherogenesis. Arterioscler. Thromb. Vasc. Biol. 15:551–561.

    PubMed  CAS  Google Scholar 

  2. Glass, C.K., and Witztum, J.L. (2001). Atherosclerosis. the road ahead. Cell 104: 503–516.

    PubMed  CAS  Google Scholar 

  3. Libby, P., Ridker, P.M., and Maseri, A. (2002). Inflammation and atherosclerosis. Circulation 105:1135–1143.

    PubMed  CAS  Google Scholar 

  4. Six, D.A., and Dennis, E.A. (2000). The expanding superfamily of phospholipase A (2) enzymes: classification and characterization. Biochim. Biophys. Acta 1488:1–19.

    PubMed  CAS  Google Scholar 

  5. Sparrow, C.P., Parthasarathy, S., and Steinberg, D. (1988). Enzymatic modification of flow density lipoprotein by purdied lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J. Lipid Res. 29:745–753.

    PubMed  CAS  Google Scholar 

  6. Sakai, M., Miyazaki, A., Hakamata, H., Sasaki, T., Yui, S., Yamazaki, M., et al. (1994). Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. J. Biol. Chem. 269:31,430–31,435.

    CAS  Google Scholar 

  7. Needleman, P., Turk, J., Jakschik, B.A., Morrison, A.R., and Lefkowith, J.B. (1986). Arachidonic acid metabolism. Annu. Rev. Biochem. 55:69–102.

    PubMed  CAS  Google Scholar 

  8. Smith, W.L., Garavito, R.M., and DeWitt, D.L. (1996). Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and-2. J. Biol. Chem., 271:33,157–33,160.

    CAS  Google Scholar 

  9. Hanasaki, K., and Arita, H. (1999). Biological and pathological functions of phospholipase A(2) receptor. Arch. Biochem. Biophys. 372:215–223.

    PubMed  CAS  Google Scholar 

  10. Hanasaki, K. (2004). Mammalian phospholipase A2:phospholipase A2 receptor. Biol. Pharm. Bull. 27:1165–1167.

    PubMed  CAS  Google Scholar 

  11. Kanemasa, T., Hanasaki, K., and Arita, H. (1992). Migration of vascular smooth muscle cells by phospholipase A2 via specific binding sites. Biochim. Biophys. Acta 11125: 210–214.

    Google Scholar 

  12. Houliston, R.A., and Wheeler-Jones, C.P. (2001). sPLA(2) cooperates with cPLA(2)alpha to regulate prostacyclin synthesis in human endothelial cells. Biochem. Biophys. Res. Commun. 287:881–887.

    PubMed  CAS  Google Scholar 

  13. Dennis, E.A. (1997). The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem. Sci. 22:1–2.

    PubMed  CAS  Google Scholar 

  14. Dennis, E.A. (2000). Phospholipase A2 in eicosanoid generation. Am. J. Respir. Crit. Care Med. 161:S32-S35

    PubMed  CAS  Google Scholar 

  15. Scott, D.L., White, S.P., Otwinowski, Z., Yuan, W., Gelb, M.H., and Sigler, P.B. (1990). Interfacial catalysis: the mechanism of phospholipase A2. Science 250:1541–1546.

    PubMed  CAS  Google Scholar 

  16. Scott, D.L., and Sigler, P.B. (1994). Structure and catalytic mechanism of secretory phospholipases A2. Adv. Protein Chem. 45:53–88.

    PubMed  CAS  Google Scholar 

  17. Lee, B.I., Yoon, E.T., and Cho, W. (1996). Roles of surface hydrophobic residues in the interfacial catalysis of bovine pancreatic phospholipase A2. Biochemistry 35: 4231–4240.

    PubMed  CAS  Google Scholar 

  18. Han, S.K., Yoon, E.T., Scott, D.L., Sigler, P.B., and Cho, W. (1997). Structural aspects of interfacial adsorption. A crystallographic and site-directed mutagenesis study of the phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. J. Biol. Chem. 272:3573–3582.

    PubMed  CAS  Google Scholar 

  19. Snitko, Y., Koduri, R.S., Han, S.K., Othman, R., Baker, S.F., Molini, B.J., et al. (1997). Mapping the interfacial binding surface of human secretory group IIa phospholipase A2. Biochemistry 36:14,325–14,333.

    CAS  Google Scholar 

  20. Bittova, L., Sumandea, M., and Cho, W. (1999). A structure-function study of the C2 domain of cytosolic phospholipase A2. Identification of essential calcium ligands and hydrophobic membrane binding residues. J. Biol. Chem. 274:9665–9672.

    PubMed  CAS  Google Scholar 

  21. Han, S.K., Kim, K.P., Koduri, R., Bittova, L., Munoz, N.M., Leff, A.R., et al. (1999). Roles of Trp3l inhigh membrane binding and proinflammatory activity of human group V phospholipase A2. J. Biol. Chem., 274:11,881–11,888.

    CAS  Google Scholar 

  22. Baker, S.F., Othman, R., and Wilton, D.C. (1998). Tryptophan-containing mutant of human (group IIa) secreted phospholipase A2 has a dramatically increased ability to hydrolyze phosphatidylcholine vesicles and cell membranes. Biochemistry 37:13,203–13,211.

    CAS  Google Scholar 

  23. Gelb, M.H., Cho, W., and Wilton, D.C. (1999). Interfacial binding of secreted phospholipases A(2): more than electrostatics and a major role for tryptophan. Curr. Opin. Struct. Biol. 9:428–432.

    PubMed  CAS  Google Scholar 

  24. Kramer, R.M., Hession, C., Johansen, B., Hayes, G., McGray, P., Chow, E.P., et al. (1989). Structure and properties of a human non-pancreatic phospholipase A2. J. Biol. Chem. 264:5768–5775.

    PubMed  CAS  Google Scholar 

  25. Minami, T., Tojo, H., Shinomura, Y., Matsuzawa, Y., and Okamoto, M. (1993). Purification and characterization of a phospholipase A2 from human ileal mucosa. Biochim. Biophys. Acta 1170:125–130.

    PubMed  CAS  Google Scholar 

  26. Murakami, M., Nakatani, Y., Atsumi, G., Inoue, K., and Kudo, I. (1997). Regulatory functions of phospholipase A2. Crit. Rev. Immunol. 17:225–283.

    PubMed  CAS  Google Scholar 

  27. Nevalainen, T.J., Gronroos, J.M., and Kallajoki, M. (1995). Expression of group II phospholipase A2 in the human gastrointestinal tract. Lab. Invest. 72:201–208.

    PubMed  CAS  Google Scholar 

  28. Nevalainen, T.J., Meri, K.M., and Niemi, M. (1993). Synovial-type (group II) phospholipase A2 human seminal plasma. Andrologia 25:355–358.

    PubMed  CAS  Google Scholar 

  29. Nevalainen, T.J., Marki, F., Kortesuo, P.T., Grutter, M.G., Di Marco, S., and Schmitz, A. (1993). Synovial type (group II) phospholipase A2 in cartilage. J. Rheumatol. 20:325–330.

    PubMed  CAS  Google Scholar 

  30. Aitken, M.A., Thomas, T., Brennecke, S.P., Scott, K.F., and Rice, G.E. (1996). Localization of type II phospholipase A2 messenger RNA and immunoactivity in human placenta and fetal membranes. Placenta 17:423–429.

    PubMed  CAS  Google Scholar 

  31. Rice, G.E., Wong, M.H., Farrugia, W., and Scott, K.F., (1998). Contribution of type II phospholipase A2 to in vitro phospholipase A2 enzymatic activity in human term placenta. J. Endocrinol. 157:25–31.

    PubMed  CAS  Google Scholar 

  32. Kurihara, H., Nakano, T., Takasu, N., and Arita, H. (1991). Intracellular localization of group II phospholipase A2 in rat vascular smooth muscle cells and its possible relationship to eicosanoid formation. Biochim. Biophys. Acta 1082: 285–292.

    PubMed  CAS  Google Scholar 

  33. Murakami, M., Kudo, I., and Inoue, K. (1993). Molecular nature of phospholipases A2 involved in prostaglandin I2 synthesis in human umbilical vein endothelial cells. Possible participation of cytosolic and extracellular type II phospholipases A2. J. Biol. Chem. 268:839–844.

    PubMed  CAS  Google Scholar 

  34. Rosenthal, M.D., Gordon, M.N., Buescher, E.S., Slusser, J.H., Harris, L.K., and Franson, R.C. (1995). Human neutrophils store type II 14-kDa phospholipase A2 in granules and secrete active enzyme in response to soluble stim-uli. Biochem. Biophys. Res. Commun. 208:650–656.

    PubMed  CAS  Google Scholar 

  35. Barnette, M.S., Rush, J., Marshall, L.A., Foley, J.J., Schmidt, D.B., et al. (1994). Effects of scalaradial, a novel inhibitor of 14 kDa phospholipase A2, on human neutrophil function. Biochem. Pharmacol. 47:1661–1667.

    PubMed  CAS  Google Scholar 

  36. Murakami, M., Kudo, I., Umeda, M., Matsuzawa, A., Takeda, M., Komada, M., et al. (1992). Detection of three distinct phospholipases A2 in cultured mast cells. J. Biochem. (Tokyo) 111:175–181.

    CAS  Google Scholar 

  37. Reddy, S.T., and Herschman, H.R. (1996). Transcellular prostaglandin production following mast cell activation is mediated by proximal secretory phospholipase A2 and distal prostaglandin synthase 1. J. Biol. Chem. 271:186–191.

    PubMed  CAS  Google Scholar 

  38. Crowl, R.M., Stoller, T.J., Conroy, R.R., and Stoner, C.R. (1991). Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. J. Biol. Chem. 266:2647–2651.

    PubMed  CAS  Google Scholar 

  39. Barbour, S.E., and Dennis, E.A. (1993). Antisense inhibition of group II phospholipase A2 expression blocks the production of prostaglandin E2 by P388D1 cells. J. Biol. Chem. 268:21,875–21,882.

    CAS  Google Scholar 

  40. Vial, D., Senorale-Pose, M., Havet, N., Molio, L., Vargaftig, B.B., and Touqui, L. (1995). Expression of the type-II phospholipase A2 in alveolar macrophages. Down-regulation by an inflammatory signal. J. Biol. Chem. 270: 17,327–17,332.

    CAS  Google Scholar 

  41. Anthonsen, M.W., Stengel, D., Hourton, D., Ninio, E., and Johansen, B. (2000). Mildly oxidized LDL induces expression of group IIa secretory phospholipase A(2) in human monocyte-derived macrophages. Arterioscler. Thromb. Vasc. Biol. 20:1276–1282.

    PubMed  CAS  Google Scholar 

  42. Menschikowski, M., Kasper, M., Lattke, P., Schiering, A., Schiefer, S., Stockinger, H., et al. (1995). Secretory group II phospholipase A2 in human atherosclerotic plaques. Atherosclerosis 118:173–181.

    PubMed  CAS  Google Scholar 

  43. Elinder, L.S., Dumitrescu, A., Larsson, P., Hedin, U., Frostegard, J., and Claesson, H.E. (1997). Expression of phospholipase A2 isoforms in human normal and athero-sclerotic arterial wall. Arterioscler. Thromb. Vasc. Biol. 17:2257–2263.

    PubMed  CAS  Google Scholar 

  44. Balboa, M.A., Balsinde, J., Winstead, M.V., Tischfield, J.A., and Dennis, E.A. (1996) Novel group V phospholipase A2 involved in arachidonic acid mobilization in murine P388D1 macrophages. J. Biol. Chem. 271:32,381–32,384.

    CAS  Google Scholar 

  45. Tischfield, J.A. (1997). A reassessment of the low molecular weight phospholipase A2 gene family in mammals. J. Biol. Chem. 272:17,247–17,250.

    CAS  Google Scholar 

  46. Vadas, P., and Pruzanski, W. (1993). Induction of group II phospholipase A2 expression and pathogenesis of the sepsis syndrome. Circ. Shock 39:160–167.

    PubMed  CAS  Google Scholar 

  47. Pruzanski, W., Keystone, E.C., Sternby, B., Bombardier, C., Snow, K.M., and Vadas, P. (1988). Serum phospholipase A2 correlates with disease activity in rheumatoid arthritis. J. Rheumatol. 15:1351–1355.

    PubMed  CAS  Google Scholar 

  48. Rader, D.J. (2000). Inflammatory markers of coronary risk. N. Engl. J. Med. 343:1179–1182.

    PubMed  CAS  Google Scholar 

  49. Murakami, M., Kambe, T., Shimbara, S., Yamamoto, S., Kuwata, H., and Kudo, I. (1999). Functional association of type IIA secretory phospholipase A(2) with the glycosyl-phosphatidylinositol-anchored heparan sulfate proteoglycan in the cyclooxygenase-2-mediated delayed prostanoidbiosynthetic pathway. J. Biol. Chem. 274:29,927–29,936.

    CAS  Google Scholar 

  50. Flood, C., Gustafsson, M., Pitas, R.E., Arnaboldi, L., Walzem, R.L., and Boren, J. (2004). Molecular mechanism for changes in proteoglycan binding on compositional changes of the core and the surface of low-density lipoprotein-containing human apolipoprotein B100. Arterioscler. Thromb. Vasc. Biol. 24:564–570.

    PubMed  CAS  Google Scholar 

  51. Sartipy, P., Johansen, B., Gasvik, K., and Hurt-Camejo, E. (2000). Molecular basis for the association of group IIA phospholipase A(2) and decorin in human atherosclerotic lesions. Circ. Res. 86:707–714.

    PubMed  CAS  Google Scholar 

  52. Kugiyama, K., Ota, Y., Sugiyama, S., Kawano, H., Doi, H., Soejima, H., et al. (2000). Prognostic value of plasma levels of secretory type II phospholipase A2 in patients with unstable angina pectoris. Am. J. Cardiol. 86:718–722.

    PubMed  CAS  Google Scholar 

  53. Couturier, C., Brouillet, A., Couriaud, C., Koumanov, K., Bereziat, G., and Andreani, M. (1999). Interleukin 1 beta induces type II-secreted phospholipase A(2) gene in vascular smooth muscle cells by a nuclear factor kappaB and peroxisome proliferator-activated receptor-mediated process. J. Biol. Chem. 274:23,085–23,093.

    CAS  Google Scholar 

  54. Antonio, V., Brouillet, A., Janvier, B., Monne, C., Bereziat, G., Andreani, M., et al. (2002). Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and interleukin-1 beta in vascular smooth muscle cells: interplay of the CCAAT/enhancer binding protein (C/EBP), nuclear factor-kappaB and Ets transcription factors. Biochem. J. 368:415–424.

    PubMed  CAS  Google Scholar 

  55. Pfeilschifter, J., Schalkwijk, C., Briner, V.A., and van den Bosch, H. (1993). Cytokine-stimulated secretion of group II phospholipase A2 by rat mesangial cells. Its contribution to arachidonic acid release and prostaglandin synthesis by cultured rat glomerular cells. J. Clin. Invest. 92: 2516–2523.

    PubMed  CAS  Google Scholar 

  56. Grass, D.S., Felkner, R.H., Chiang, M.Y., Wallace, R.E., Nevalainen, T.J., Bennett, C.F., et al. (1996). Expression of human group IIPLA2 in transgenic mice results in epidermal hyperplasia in the absence of inflammatory infiltrate. J. Clin. Invest. 97:2233–2241.

    PubMed  CAS  Google Scholar 

  57. Murakami, M., Koduri, R.S., Enomoto, A., Shimbara, S., Seki, M., Yoshihara, K., et al. (2001). Distinct arachidonate-releasing functions of mammalian secreted phospholipase A2s in human embryonic kidney 293 and rat mastocytoma RBL-2H3 cells through heparan sulfate shuttling and external plasma membrane mechanisms. J. Biol. Chem. 276:10,083–10,096.

    CAS  Google Scholar 

  58. Murakami, M., Naraba, H., Tanioka, T., Semmyo, N., Nakatani, Y., Kojima, F., et al. (2000). Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J. Biol. Chem. 275:32,783–32,792.

    CAS  Google Scholar 

  59. Bezzinc, S., Koduri, R.S., Valentin, E., Murakami, M., Kudo, I., Ghomashchi, F., et al. (2000). Exogenously added human group X secreted phospholipase A(2) but not the group IB, IIA, and V enzymes efficiently release arachidonic acid from adherent mammalian cells. J. Biol. Chem. 275:3179–3191.

    Google Scholar 

  60. Enomoto, A., Murakami, M., Valentin, E., Lambeau, G., Gelb, M.H., et al. (2000). Redundant and segregated functions of granule-associated heparin-binding group II sub-family of secretory phospholipases A2 in the regulation of degranulation and prostaglandin D2 synthesis in mast cells. J. Immunol. 165:4007–4014.

    PubMed  CAS  Google Scholar 

  61. Laine, V.J., Grass, D.S., and Nevalainen, T.J. (1999). Protection by group II phospholipase A2 against Staphylococcus aureus. J. Immunol. 162:7402–7408.

    PubMed  CAS  Google Scholar 

  62. Qu, X.D. and Lehrer, R.I. (1998). Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears. Infect. Immun. 66:2791–2797.

    PubMed  CAS  Google Scholar 

  63. Kennedy, B.P., Payette, P., Mudgett, J., Vadas, P., Pruzanski, W., Kwan, M., et al. (1995). A natural disruption of the secretory group II phospholipase A2 gene in inbred mouse strains. J. Biol. Chem. 270:22,378–22,385.

    CAS  Google Scholar 

  64. MacPhee, M., Chepenik, K.P., Liddell, R.A., Nelson, K.K., Siracusa, L.D., and Buchberg, A.M. (1995). The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell 81:957–966.

    PubMed  CAS  Google Scholar 

  65. Gould, K.A. and Dove, W.F. (1997). Localized gene action controlling intestinal neoplasia in mice. Proc. Natl. Acad. Sci. USA 94:5848–5853.

    PubMed  CAS  Google Scholar 

  66. Dove, W.F., Cormier, R.T., Gould, K.A., Halberg, R.B., Merritt, A.J., Newton, M.A., et al. (1998). The intestinal epithelium and its neoplasms: genetic, cellular and tissue interactions. Philos. Trans. R. Soc. Lond. B Biol. Sci. 353:915–923.

    PubMed  CAS  Google Scholar 

  67. Ivandic, B., Castellani, L.W., Wang, X.P., Qiao, J.H., Mehrabian, M., Navab, M., et al. (1999). Role of group II secretory phospholipase A2 in atherosclerosis: 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Arterioscler. Thromb. Vasc. Biol. 19:1284–1290.

    PubMed  CAS  Google Scholar 

  68. Webb, N.R., Bostrom, M.A., Szilvassy, S.J., van der Westhuyzen, D.R., Daugherty, A., and de Beer, F.C. (2003). Macrophage-expressed group IIA secretory phospholipase A2 increases ather osclerotic lesion formation in LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 23:263–268.

    PubMed  CAS  Google Scholar 

  69. Ghesquiere, S.A., Gijbels, M.J., Anthonsen, M., van Gorp, P.J., van der Made, I., Johansen, B., et al. (2005). Macrophage-specific overex pression of group IIa sPLA2 results in increased atherosclerotic lesion size and enhanced collagen deposition. J. Lipid Res. 46:201–210.

    PubMed  CAS  Google Scholar 

  70. Sawada, H., Murakami, M., Enomoto, A., Shimbara, S., and Kudo, I. (1999). Regulation of type V phospholipase A2 expression and function by proinflammatory stimuli. Eur. J. Biochem. 263:826–835.

    PubMed  CAS  Google Scholar 

  71. Murakami, M., Shimbara, S., Kambe, T., Kuwata, H., Winstead, M.V., Tischfield, J.A., et al. (1998). The functions of five distinct mammalian phospholipase A2S in regulating arachidonic acid release. Type IIa and type V secretory phospholipase A2S are functionally redundant and act in concert with cytosolic phospholipase A2. J. Biol. Chem. 273:14,411–14,423.

    CAS  Google Scholar 

  72. Murakami, M., Kambe, T., Shimbara, S., Higashino, K., Hanasaki, K., Arita, H., et al. (1999). Different functional aspects of the group II subfamily (Types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic acid release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation. J. Biol. Chem. 274:31,435–31,444.

    CAS  Google Scholar 

  73. Kim, Y.J., Kim, K.P., Rhee, H.J., Das, S., Rafter, J.D., Oh, Y.S., et al. (2002). Internalized group V secretory phospholipase A2 acts on the perinuclear membranes. J. Biol. Chem. 277:9358–9365.

    PubMed  CAS  Google Scholar 

  74. Tischfield, J.A., Xia, Y.R., Shih, D.M., Klisak, I., Chen, J., Engle, S.J., et al. (1996). Low-molecular-weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and human. genomics 32:328–333.

    PubMed  CAS  Google Scholar 

  75. Pan, Y.H., Yu, B.Z., Singer, A.G., Ghomashchi, F., Lambeau, G., Gelb, M.H., et al. (2002). Crystal structure of human group X secreted phospholipase A2. Electrostatically neutral interfacial surface targets zwitterionic mem-branes. J. Biol. Chem. 277:29,086–29,093.

    CAS  Google Scholar 

  76. Murakami, M., Masuda, S., Shimbara, S., Bezzine, S., Lazdunski, M., Lambeau, G., et al. (2003). Cellulararachidonate-releasing function of novel classes of secretory phospholipase A2s (groups III and XII). J. Biol. Chem. 278:10,657–10,667.

    CAS  Google Scholar 

  77. Gesquiere, L., Cho, W., and Subbaiah, P.V. (2002). Role of group IIa and group V secretory phospholipases A(2) in the metabolism of lipoproteins. Substrate specificities of the enzymes and the regulation of their activities by sphingomyelin. Biochemistry 41:4911–4920.

    PubMed  CAS  Google Scholar 

  78. Gronroos, J.O., Laine, V.J., Janssen, M.J., Egmond, M.R., and Nevalainen, T.J. (2001). Bactericidal properties of group IIA and group V phospholipases A2. J Immunol. 166:4029–4034.

    PubMed  CAS  Google Scholar 

  79. Chen, J., Engle, S.J., Seilhamer, J.J., and Tischfield, J.A. (1994). Cloning, expression and partial characterization of a novel rat phospholipase A2. Biochim. Biophys. Acta 1215:115–120.

    PubMed  CAS  Google Scholar 

  80. Chen, J., Engle, S.J., Seilhamer, J.J., and Tischfield, J.A. (1994). Cloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2. J. Biol. Chem. 269:2365–2368.

    PubMed  CAS  Google Scholar 

  81. Wooton-Kee, C.R., Boyanovsky, B.B., Nasser, M.S., de Villiers, W.J., and Webb, N.R. (2004). Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous particle aggregation and promotes macrophage foam cell formation. Arterioscler. Thromb. Vasc. Biol. 24:762–767.

    PubMed  CAS  Google Scholar 

  82. Evangelou, A.M. (1994). Platelet-activating factor (PAF): implications for coronary heart and vascular diseases. Prostaglandins Leukot. Essent. Fatty Acids 50:1–28.

    PubMed  CAS  Google Scholar 

  83. Imaizumi, T.A., Stafforini, D.M., Yamada, Y., McIntyre, T.M., Prescott, S.M., and Zimmerman, G.A. (1995). Platelet-activating factor: a mediator for clinicians. J. Intern. Med. 238:5–20.

    PubMed  CAS  Google Scholar 

  84. Farr, R.S., Cox, C.P., Wardlow, M.L., and Jorgensen, R. (1980). Preliminary studies of an acid-labile factor (ALF) in human sera that inactivates platelet-activating factor (PAF). Clin. Immunol. Immunopathol. 15:318–330.

    PubMed  CAS  Google Scholar 

  85. Hakkinen, T., Luoma, J.S., Hiltunen, M.O., Macphee, C.H., Milliner, K.J., Patel, L., et al. (1999). Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 19:2909–2917.

    PubMed  CAS  Google Scholar 

  86. Asano, K., Okamoto, S., Fukunaga, K., Shiomi, T., Mori, T., Iwata, M., et al. (1999). Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma. Biochem. Biophys. Res. Commun. 261:511–514.

    PubMed  CAS  Google Scholar 

  87. Tjoelker, L.W., Wilder, C., Eberhardt, C., Stafforini, D.M., Dietsch, G., Schimpf, B., et al. (1995). Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature 374:549–553.

    PubMed  CAS  Google Scholar 

  88. Tjoelker, L.W., Eberhardt, C., Unger, J., Trong, H.L., Zimmerman, G.A., McIntyre, T.M., et al. (1995). Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad. J. Biol. Chem. 270:25,481–25,487.

    CAS  Google Scholar 

  89. Stafforini, D.M., Prescott, S.M., and McIntyre, T.M. (1987). Human plasma platelet-activating factor acetylhydrolase. Purification and properties. J. Biol. Chem. 262:4223–4230.

    PubMed  CAS  Google Scholar 

  90. Wardlow, M.L., Cox, C.P., Meng, K.E., Greene, D.E., and Farr, R.S. (1986). Substrate specificity and partial characterization of the PAF-acylhydrolase in human serum that rapidly inactivates platelet-activating factor. J. Immunol. 136:3441–3446.

    PubMed  CAS  Google Scholar 

  91. Imaizumi, T. (1996). The fate of platelet-activating factor: PAF acetylhydrolases from plasma and tissues. In Lipobiology (Gross, R., ed.), JAI Press, CT, pp. 141–162.

    Google Scholar 

  92. Noto, H., Hara, M., Karasawa, K., Iso, O.N., Satoh, H., Togo, M., et al. (2003). Human plasma platelet-activating factor acetylhydrolase binds to all the murine lipoproteins, conferring protection against oxidative stress. Arterioscler. Thromb. Vasc. Biol. 23:829–835.

    PubMed  CAS  Google Scholar 

  93. Steinbrecher, U.P. and Pritchard, P.H. (1989). Hydrolysis of phosphatidylcholine during LDL oxidation is mediated by platelet-activating factor acetylhydrolase. J. Lipid Res. 30:305–315.

    PubMed  CAS  Google Scholar 

  94. Stremler, K.E., Stafforini, D.M., Prescott, S.M., and McIntyre, T.M. (1991). Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates. J. Biol. Chem. 266:11,095–11,103.

    CAS  Google Scholar 

  95. Stremler, K.E., Stafforini, D.M., Prescott, S.M., Zimmerman, G.A., and McIntyre, T.M. (1989). An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma. J. Biol. Chem. 264:5331–5334.

    PubMed  CAS  Google Scholar 

  96. Min, J.H., Wilder, C., Aoki, J., Arai, H., Inoue, K., Paul, L., et al. (2001). Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme. Biochemistry 40:4539–4549.

    PubMed  CAS  Google Scholar 

  97. Liu, M. and Subbaiah, P.V. (1994). Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase. Proc. Natl. Acad. Sci. USA 91:6035–6039.

    PubMed  CAS  Google Scholar 

  98. Tsoukatos, D.C., Liapikos, T.A., Tselepis, A.D., Chapman, M.J., and Ninio, E. (2001). Platelet-activating factor acetylhydrolase and transacetylase activities in human plasma low-density lipoprotein. Biochem. J. 357:457–464.

    PubMed  CAS  Google Scholar 

  99. Tselepis, A.D., Dentan, C., Karabina, S.A., Chapman, M.J., and Ninio, E. (1995). PAF-degrading acetylhydrolase is preferentially associated with dense LDL and VHDL-1 in human plasma. Catalytic characteristics and relation to the monocyte-derived enzyme. Arterioscler. Thromb. Vasc. Biol. 15:1764–1773.

    PubMed  CAS  Google Scholar 

  100. Caslake, M.J., Packard, C.J., Suckling, K.E., Holmes, S.D., Chamberlain, P., and Macphee, C.H. (2000). Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 150:413–419.

    PubMed  CAS  Google Scholar 

  101. Tsaoussis, V. and Vakirtzi-Lemonias, C. (1994). The mouse plasma PAF acetylhydrolase: II. It consists of two enzymes both associated with the HDL. J. Lipid Mediators Cell Signalling 9:317–331.

    CAS  Google Scholar 

  102. Rodrigo, L., Mackness, B., Durrington, P.N., Hernandez, A., and Mackness, M.I. (2001). Hydrolysis of platelet-activating factor by human serum paraoxonase. Biochem. J. 354:1–7.

    PubMed  CAS  Google Scholar 

  103. Glomset, J.A. (1968). The plasma lecithins: cholesterol acyltransferase reaction. J. Lipid Res. 9:155–167.

    PubMed  CAS  Google Scholar 

  104. Aron, L., Jones, S., and Fielding, C.J. (1978). Human plasmalecithin-cholesterol acyltransferase. Characterization of cofactor-dependent phospholipase activity. J. Biol. Chem. 253:7220–7226.

    PubMed  CAS  Google Scholar 

  105. McCall, M.R., van den Berg, J.J., Kuypers, F.A., Tribble, D.L., Krauss, R.M., Knoff, L.J., et al. (1994). Modification of LCAT activity and HDL structure. New links between cigarette smoke and coronary heart disease risk. Arterioscler. Thromb. 14:248–253.

    PubMed  CAS  Google Scholar 

  106. Subbaiah, P.V. and Liu, M. (1996). Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids. Biochim. Biophys. Acta 1301:115–126.

    PubMed  Google Scholar 

  107. Chisolm, G.M. and Steinberg, D. (2000). The oxidative modification hypothesis of atherogenesis: an overview. Free Radic. Biol. Med. 28:1815–1826.

    PubMed  CAS  Google Scholar 

  108. Quarck, R., De Geest, B., Stengel, D., Mertens, A., Lox, M., Theilmeier, G., et al. (2001). Adenovirus-mediated gene transfer of human platelet-activating factor-acetyl-hydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice. circulation 103:2495–2500.

    PubMed  CAS  Google Scholar 

  109. Min, J.H., Jain, M.K., Wilder, C., Paul, L., Apitz-Castro, R., Aspleaf, D.C. et al. (1999). Membrane-bound plasma platelet activating factor acetylhydrolase acts on substrate in the aqueous phase. Biochemistry 38:12,935–12,942.

    CAS  Google Scholar 

  110. MacPhee, C.H., Moores, K.E., Boyd, H.F., Dhanak, D., Ife, R.J., Leach, C.A., et al. (1999). Lipoprotein-associated phospholipase A2, platelet-activating factor acetyl-hydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. Biochem. J. 338 (Pt. 2):479–487.

    PubMed  CAS  Google Scholar 

  111. Packard, C.J., O'Reilly, D.S., Caslake, M.J., McMahon, A.D., Ford, I., Cooney, J., et al. (2000). Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 343:1148–1155.

    PubMed  CAS  Google Scholar 

  112. Tselepis, A.D. and John Chapman, M. (2002). Inflammation, bioactive lipids and atherosclerosis: potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. Atheroscler. Suppl. 3:57–68.

    PubMed  CAS  Google Scholar 

  113. Cupillard, L., Koumanov, K., Mattei, M.G., Lazdunski, M., and Lambeau, G. (1997). Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2. J. Biol. Chem. 272:15,745–15,752.

    CAS  Google Scholar 

  114. Hanasaki, K., Ono, T., Saiga, A., Morioka, Y., Ikeda, M., Kawamoto, K., et al. (1999). Purified group X secretory phospholipase A(2) induced prominent release of arachidonic acid from human myeloid leukemia cells. J. Biol. Chem. 274:34,203–34,211.

    CAS  Google Scholar 

  115. Morioka, Y., Saiga, A., Yokota, Y., Suzuki, N., Ikeda, M., Ono, T., et al. (2000). Mouse group X secretory phospholipase A2 induces a potent release of arachidonic acid from spleen cells and acts as a ligand for the phospholipase A2 receptor. Arch. Biochem. Biophys. 381:31–42.

    PubMed  CAS  Google Scholar 

  116. van Eijk, J.H., Verheij, H.M., Dijkman, R., and de Haas, G.H. (1983). Interaction of phospholipase A2 from Naja melanoleucasnake venom with monomeric substrate analogs. Activation of the enzyme by protein-protein or lipid-protein interactions. Eur. J. Biochem. 132:183–188.

    PubMed  Google Scholar 

  117. Jain, M.K., Egmond, M.R., Verheij, H.M., Apitz-Castro, R., Dijkman, R., and De Haas, G.H. (1982). Interaction of phospholipase A2 and phospholipid bilayers. Biochim. Biophys. Acta 688:341–348.

    PubMed  CAS  Google Scholar 

  118. Singer, A.G., Ghomashchi, F., Le Calvez, C., Bollinger, J., Bezzine, S., Rouault, M., et al. (2002). Interfacial kinetic and binding properties of the complete set of human and mouse groups I, II, V, X, and XII secreted phospholipases A2. J. Biol. Chem. 277:48,535–48,549.

    CAS  Google Scholar 

  119. Hanasaki, K., Yamada, K., Yamamoto, S., Ishimoto, Y., Saiga, A., Ono, T., et al. (2002). Potent modification of low density lipoprotein by group X secretory phospholipase A2 is linked to macrophage foam cell formation. J. Biol. Chem. 277:29,116–29,124.

    CAS  Google Scholar 

  120. Murakami, M. and Kudo, I. (2004). Secretory phospholipase A2. Biol. Pharm. Bull. 27:1158–1164.

    PubMed  CAS  Google Scholar 

  121. Kim, K.P., Rafter, J.D., Bittova, L., Han, S.K., Snitko, Y., Munoz, N.M., et al. (2001). Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J. Biol. Chem. 276:11,126–11,134.

    CAS  Google Scholar 

  122. Saiga, A., Morioka, Y., Ono, T., Nakano, K., Ishimoto, Y., Arita, H., et al. (2001). Group X secretory phospholipase A(2) induces potent productions of various lipid mediators in mouse peritoneal macrophages. Biochim. Biophys. Acta 1530:67–76.

    PubMed  CAS  Google Scholar 

  123. Morioka, Y., Ikeda, M., Saiga, A., Fujii, N., Ishimoto, Y., Arita, H., et al. (2000). Potential role of group X secretory phospholipase A(2) in cyclooxygenase-2-dependent PGE (2) formation during colon tumorigenesis. FEBS Lett 487:262–266.

    PubMed  CAS  Google Scholar 

  124. Cupillard, L., Mulherkar, R., Gomez, N., Kadam, S., Valentin, E., Lazdunski, M., and Lambeau, G. (1999). Both group IB and group IIA secreted phospholipases A2 are natural ligands of the mouse 180-kDa M-type receptor. J. Biol. Chem. 274:7043–7051.

    PubMed  CAS  Google Scholar 

  125. Arita, H., Hanasaki, K., Nakano, T., Oka, S., Teraoka, H., and Matsumoto, K. (1991). Novel proliferative effect of phospholipase A2 in Swiss 3T3 cells via specific binding site. J. Biol. Chem. 266:19,139–19,141.

    CAS  Google Scholar 

  126. Hanasaki, K. and Arita, H. (2002). Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat. 68–69:71–82.

    PubMed  Google Scholar 

  127. Hanasaki, K., Yokota, Y., Ishizaki, J., Itoh, T., and Arita, H. (1997). Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice. J. Biol. Chem. 272:32,792–32,797.

    CAS  Google Scholar 

  128. Yokota, Y., Higashino, K., Nakano, K., Arita, H., and Hanasaki, K. (2000). Identification of group X secretory phospholipase A(2) as a natural ligand for mouse phospholipase A(2) receptor. FEBS Lett. 478:187–191.

    PubMed  CAS  Google Scholar 

  129. Yokota, Y., Notoya, M., Higashino, K., Ishimoto, Y., Nakano, K., Arita, H., et al. (2001). Clearance of group X secretory phospholipase A(2) via mouse phospholipase A(2) receptor. FEBS Lett. 509:250–254.

    PubMed  CAS  Google Scholar 

  130. Kini, R.M. and Evans, H.J. (1989). A model to explain the pharmacological effects of snake venom phospholipases A2. Toxicon 27:613–635.

    PubMed  CAS  Google Scholar 

  131. Higashino Ki, K., Yokota, Y., Ono, T., Kamitani, S., Arita, H., and Hanasaki, K. (2002). Identification of a soluble form phospholipase A2 receptor as a circulating endogenous inhibitor for secretory phospholipase A2. J. Biol. Chem. 277:13,583–13,588.

    Google Scholar 

  132. Ancian, P., Lambeau, G., Mattei, M.G., and Lazdunski, M. (1995). The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning, identification of a secreted soluble form, expression, and chromosomal localization. J. Biol. Chem. 270:8963–8970.

    PubMed  CAS  Google Scholar 

  133. Balsinde, J., Balboa, M.A., and Dennis, E.A. (1998). Functional coupling between secretory phospholipase A2 and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A2. Proc. Natl. Acad. Sci. USA 95:7951–7956.

    PubMed  CAS  Google Scholar 

  134. Balsinde, J. and Dennis, E.A. (1996). Distinct roles in signal transduction for each of the phospholipase A2 enzymes present in P388D1 macrophages. J. Biol. Chem. 271:6758–6765.

    PubMed  CAS  Google Scholar 

  135. Evans, J.H., Spencer, D.M., Zweifach, A., and Leslie, C.C. (2001). Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. J. Biol. Chem. 276:30,150–30,160.

    CAS  Google Scholar 

  136. Hirabayashi, T., Kume, K., Hirose, K., Yokomizo, T., Iino, M., Itoh, H., et al. (1999). Critical duration of intracellular Ca2+ response required for continuous translocation and activation of cytosolic phospholipase A2. J. Biol. Chem. 274:5163–5169.

    PubMed  CAS  Google Scholar 

  137. Lin, L.L., Wartmann, M., Lin, A.Y., Knopf, J.L., Seth, A., and Davis, R.J. (1993). cPLA2 is phosphorylated and activated by MAP kinase. Cell 72:269–278.

    PubMed  CAS  Google Scholar 

  138. Hefner, Y., Borsch-Haubold, A.G., Murakami, M., Wilde, J.I., Pasquet, S., Schieltz, D., et al. (2000). Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J. Biol. Chem. 275:37,542–37,551.

    CAS  Google Scholar 

  139. Wijkander, J., O'Flaherty, J.T., Nixon, A.B., and Wykle, R.L. (1995). 5-Lipoxygenase products modulate the activity of the 85-kDa phospholipase A2 in human neutrophils. J. Biol. Chem. 270:26,543–26,549.

    CAS  Google Scholar 

  140. Uozumi, N., Kume, K., Nagase, T., Nakatani, N., Ishii S., Tashiro, F., et al. (1997). Role of cytosolic phospholipase A2 in allergic response and parturition. Nature 390:618–622.

    PubMed  CAS  Google Scholar 

  141. Takaku, K., Sonoshita, M., Sasaki, N., Uozumi, N., Doi, Y., Shimizu, T., et al. (2000). Suppression of intestinal polyposis in Apc(delta 716) knockout mice by an additional mutation in the cytosolic phospholipase A(2) gene. J. Biol. Chem. 275:34,013–34,016.

    CAS  Google Scholar 

  142. Smith, W.L. and Marnett, L.J. (1991). Prostaglandin endoperoxide synthase: structure and catalysis. Biochim. Biophys. Acta 1083:1–17.

    PubMed  CAS  Google Scholar 

  143. Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A., Simon, L.S., Van De Putte, L.B., et al. (1998). Cyclooxygenase in biology and disease. FASEB J. 12:1063–1073.

    PubMed  CAS  Google Scholar 

  144. Samuelsson, B. (1983). From studies of biochemical mechanism to novel biological mediators: prostaglandin endoperoxides, thromboxanes, and leukotrienes. Nobel Lecture, 8 December 1982. Biosci. Rep. 3:791–813.

    PubMed  CAS  Google Scholar 

  145. Vane, J.R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New Biol. 231:232–235.

    PubMed  CAS  Google Scholar 

  146. Vila, L. (2004). Cyclooxygenase and 5-lipoxygenase pathways in the vessel wall: role in atherosclerosis. Med. Res. Rev. 24:399–424.

    PubMed  CAS  Google Scholar 

  147. Willoughby D.A., Moore, A.R., and Colville-Nash, P.R. (2000). COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. Lancet 355:646–648.

    PubMed  CAS  Google Scholar 

  148. Botting, R.M. (2000). Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin. Infect. Dis. 31 (Suppl. 5):S202–210.

    Google Scholar 

  149. Kim, B.H., Kang, K.S., and Lee, Y.S. (2004). Effect of retinoids on LPS-induced COX-2 expression and COX-2 associated PGE(2) release from mouse peritoneal macrophages and TNF-alpha release from rat peripheral blood mononuclear cells. Toxicol. Lett. 150:191–201.

    PubMed  CAS  Google Scholar 

  150. Guastadisegni, C., Nicolini, A., Balduzzi, M., Ajmone-Cat, M.A., and Minghetti, L. (2002). Modulation of PGE(2) and TNFalpha by nitric oxide and LPS-activated RAW 264.7 cells. Cytokine 19:175–180.

    PubMed  CAS  Google Scholar 

  151. Mitchell, J.A., Belvisi, M.G., Akarasereenont, P., Robbins, R.A., Kwon, O.J., Croxtall, J., et al. (1994). Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone. Br. J. Pharmacol. 113:1008–1014.

    PubMed  CAS  Google Scholar 

  152. Chandrasekharan, N.V., Dai, H., Roos, K.L., Evanson, N.K., Tomsik, J., Elton, T.S., et al. (2002). COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc. Natl. Acad. Sci. USA 99:13,926–13,931.

    CAS  Google Scholar 

  153. Schwab, J.M., Schluesener, H.J., and Laufer, S. (2003). COX-3: just another COX or the solitary elusive target of paracetamol? Lancet 361:981–982.

    PubMed  Google Scholar 

  154. Simon, L.S. (1999). Role and regulation of cyclooxygenase-2 during inflammation. Am. J. Med. 106:37S-42S.

    PubMed  CAS  Google Scholar 

  155. Khuri, F.R., Wu, H., Lee, J.J., Kemp, B.L., Lotan, R., Lippman, S.M., et al. (2001). Cyclooxygenase-2 over-expression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin. Cancer Res. 7:861–867.

    PubMed  CAS  Google Scholar 

  156. Meade, E.A., McIntyre, T.M., Zimmerman, G.A., and Prescott, S.M. (1999). Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells. J. Biol. Chem. 274:8328–8334.

    PubMed  CAS  Google Scholar 

  157. Baker, C.S., Hall, R.J., Evans, T.J., Pomerance, A., Maclouf, J., Creminon, C., et al. (1999). Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler. Thromb. Vasc. Biol. 19:646–655.

    PubMed  CAS  Google Scholar 

  158. Schonbeck, U., Sukhova, G.K., Graber, P., Coulter, S., and Libby, P. (1999). Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. Am. J. Pathol. 155:1281–1291.

    PubMed  CAS  Google Scholar 

  159. Belton, O., Byrne, D., Kearney, D., Leahy, A., and Fitzgerald, D.J. (2000). Cyclooxygenase-1 and 2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 102:840–845.

    PubMed  CAS  Google Scholar 

  160. Cipollone, F., Prontera, C., Pini, B., Marini, M., Fazia, M., De Cesare, D., et al. (2001). Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation 104:921–927.

    PubMed  CAS  Google Scholar 

  161. McAdam, B.F., Catella-Lawson, F., Mardini, I.A., Kapoor, S., Lawson, J.A., and FitzGerald, G.A. (1999). Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc. Natl. Acad. Sci. USA 96:272–277.

    PubMed  CAS  Google Scholar 

  162. Catella-Lawson, F., McAdam, B., Morrison, B.W., Kapoor, S., Kujubu, D., Antes, L., et al. (1999). Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J. Pharmacol. Exp. Ther. 289:735–741.

    PubMed  CAS  Google Scholar 

  163. Siegle, I., Klein, T., Zou, M.H., Fritz, P., and Komhoff, M. (2000). Distribution and cellular localization of prostacyclin synthase in human brain. J. Histochem. Cytochem. 48:631–641.

    PubMed  CAS  Google Scholar 

  164. Liou, J.Y., Shyue, S.K., Tsai, M.J., Chung, C.L., Chu, K.Y., and Wu, K.K. (2000). Colocalization of prostacyclin synthase with prostaglandin H synthase-1 (PGHS-1) but not phorbol ester-induced PGHS-2 in cultured endothelial cells. J. Biol. Chem. 275:15,314–15,320.

    CAS  Google Scholar 

  165. Korita, D., Sagawa, N., Itoh, H., Yura, S., Yoshida, M., Kakui, K., et al. (2002). Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression. J. Clin. Endocrinol. Metab. 87:5209–5219.

    PubMed  CAS  Google Scholar 

  166. Miyata, A., Hara, S., Yokoyama, C., Inoue, H., Ullrich, V., and Tanabe, T. (1994). Molecular cloning and expression of human prostacyclin synthase. Biochem. Biophys. Res. Commun. 200:1728–1734.

    PubMed  CAS  Google Scholar 

  167. Fleisher-Berkovich, S. and Danon, A. (1999). IL-1 alpha but not IL-1 beta-induced prostaglandin synthesis is inhibited by corticotropin-releasing factor. Cytokine 11:239–243.

    PubMed  CAS  Google Scholar 

  168. Chevalier, D., Cauffiez, C., Bernard, C., Lo-Guidice, J.M., Allorge, D., Fazio, F., et al. (2001). Characterization of new mutations in the coding sequence and 5′-untranslated region of the human prostacylcin synthase gene (CYP8A1). Hum. Genet. 108:148–155.

    PubMed  CAS  Google Scholar 

  169. Moncada, S., Gryglewski, R., Bunting, S., and Vane, J.R. (1976). An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665.

    PubMed  CAS  Google Scholar 

  170. Numaguchi, Y., Naruse, K., Harada, M., Osanai, H., Mokuno, S., Murase, K., et al. (1999). Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury. Arterioscler. Thromb. Vasc. Biol 19:727–733.

    PubMed  CAS  Google Scholar 

  171. Mukherjee, D., Nissen, S.E., and Topol, E.J. (2001). Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286:954–959.

    PubMed  CAS  Google Scholar 

  172. Blumenstein, M., Keelan, J.A., and Mitchell, M.D. (2001). Hypoxia attenuates PGE(2) but increases prostacyclin and thromboxane production in human term villous trophoblast. Placenta 22:519–525.

    PubMed  CAS  Google Scholar 

  173. Moncada, S. and Vane, J.R. (1979). Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N. Engl. J. Med. 300:1142–1147.

    PubMed  CAS  Google Scholar 

  174. Vane, J.R. and Botting, R.M. (1995). Pharmacodynamic profile of prostacyclin. Am. J. Cardiol. 75:3A-10A.

    PubMed  CAS  Google Scholar 

  175. Yokoyama, C., Miyata, A., Ihara, H., Ullrich, V., and Tanabe, T. (1991). Molecular cloning of human platelet thromboxane A synthase. Biochem. Biophys. Res. Commun. 178:1479–1484.

    PubMed  CAS  Google Scholar 

  176. Ohashi, K., Ruan, K.H., Kulmacz, R.J., Wu, K.K., and Wang, L.H. (1992). Primary structure of human thromboxane synthase determined from the cDNA sequence. J. Biol. Chem. 267:789–793.

    PubMed  CAS  Google Scholar 

  177. Shen, R.F. and Tai, H.H. (1998). Thromboxanes: synthase and receptors. J. Biomed. Sci. 5:153–172.

    PubMed  CAS  Google Scholar 

  178. Dusting, G.J., Moncada, S., and Vane, J. R. (1977). Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachindonic acid. Prostaglandins 13:3–15.

    PubMed  CAS  Google Scholar 

  179. Hamberg, M., Svensson, J., and Samuelsson, B. (1975). Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. USA 72:2994–2998.

    PubMed  CAS  Google Scholar 

  180. Hornby, E.J. and Skidmore, I.F. (1982). Evidence that prostaglandin endoperoxides can induce platelet aggregation in the absence of thromboxane A2 production. Biochem. Pharmacol. 31:1158–1160.

    PubMed  CAS  Google Scholar 

  181. Yamada, M., Numaguchi, Y., Okumura, K., Harada, M., Naruse, K., Matsui, H., et al. (2002). Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid synthesis and inhibits neointimal formation in rat balloon-injured arteries. Arterioscler. Thromb. Vasc. Biol. 22:256–262.

    PubMed  CAS  Google Scholar 

  182. Cheng, Y., Austin, S.C., Rocca, B., Koller, B.H., Coffman, T.M., Grosser, T., et al. (2002). Role of prostacyclin in the cardiovascular response to thromboxane A 2. Science 296: 539–541.

    PubMed  CAS  Google Scholar 

  183. Vane, J.R. and Botting, R.M. (1998). Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 47 (Suppl. 2):S78–87.

    Google Scholar 

  184. Silverstein, F.E., Faich, G., Goldstein, J.L., Simon, L.S., Pincus, T., Whelton, A., et al. (2000). Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 284:1247–1255.

    PubMed  CAS  Google Scholar 

  185. Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos-Vargas, R., Davis, B., et al. (2000). Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N. Engl. J. Med. 343:1520–1528.

    PubMed  CAS  Google Scholar 

  186. Konstam, M.A., Weir, M.R., Reicin, A., Shapiro, D., Sperling, R.S., Barr, E., et al., (2001). Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. Circulation 104:2280–2288.

    PubMed  CAS  Google Scholar 

  187. Graham, D.J. (2004). Risk of acute infaction and sudden cardiac death in patients treated with COX-2 selective and non-selective NSAIDs. In Inflammopharmacology: Office of Drug Safety.

  188. FitzGerald, G.A. (2003). COX-2 and beyond: Approaches to prostaglandin inhibition in human disease. Nat. Rev. Drug Discov. 2:879–890.

    PubMed  CAS  Google Scholar 

  189. Juni, P., Nartey, L., Reichenbach, S., Sterchi, R., Dieppe, P.A., and Egger, M. (2004). Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 364: 2021–2029.

    PubMed  CAS  Google Scholar 

  190. Solomon, D.H., Glynn, R.J., Levin, R., and Avorn, J. (2002). Nonsteroidal anti-inflammatory drug use and acute myocardial infarction. Arch. Intern. Med. 162:1099–1104.

    PubMed  CAS  Google Scholar 

  191. Watson, D.J., Rhodes, T., Cai, B., and Guess, H.A. (2002). Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch. Intern. Med. 162:1105–1110.

    PubMed  CAS  Google Scholar 

  192. Rahme, E., Pilote, L., and LeLorier, J. (2002). Association between naproxen use and protection against acute myocardial infarction. Arch. Intern. Med. 162:1111–1115.

    PubMed  CAS  Google Scholar 

  193. Bea, F., Blessing, E., Bennett, B.J., Kuo, C.C., Campbell, L.A., Kreuzer, J., et al. (2003). Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis. Cardiovasc. Res. 60:198–204.

    PubMed  CAS  Google Scholar 

  194. Belton, O.A., Duffy, A., Toomey, S., and Fitzgerald, D.J. (2003). Cyclooxygenase isoforms and platelet vessel wall interactions in the apolipoprotein E knockout mouse model of atherosclerosis. Circulation 108:3017–3023.

    PubMed  CAS  Google Scholar 

  195. Qi, Z., Hao, C.M., Langenbach, R.I., Breyer, R.M., Redha, R., Morrow, J.D., et al. (2002). Opposite effects of cyclooxygenase-1 and-2 activity on the pressor response to angiotensin II. J. Clin. Invest. 110:61–69.

    PubMed  CAS  Google Scholar 

  196. Morham, S.G., Langenbach, R., Loftin, C.D., Tiano, H.F., Vouloumanos, N., Jennette, J.C., et al. (1995). Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 83:473–482.

    PubMed  CAS  Google Scholar 

  197. Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., and Kudo, I. (2000). Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J. Biol. Chem. 275:32,775–32,782.

    CAS  Google Scholar 

  198. Jakobsson, P.J., Thoren, S., Morgenstern, R., and Samuelsson, B. (1999). Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc. Natl. Acad. Sci. USA 96:7220–7225.

    PubMed  CAS  Google Scholar 

  199. Forsberg, L., Leeb, L., Thoren, S., Morgenstern, R., and Jakobsson, P. (2000). Human glutathione dependent prostaglandin E synthase: gene structure and regulation. FEBS Lett. 471:78–82.

    PubMed  CAS  Google Scholar 

  200. Stichtenoth, D.O., Thoren, S., Bian, H., Peters-Golden, M., Jakobsson, P.J., and Crofford, L.J. (2001). Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. J. Immunol. 167:469–474.

    PubMed  CAS  Google Scholar 

  201. Naraba, H., Yokoyama, C., Tago, N., Murakami, M., Kudo, I., Fueki, M., et al. (2002). Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Essential role of the transcription factor Egr-1. J. Biol. Chem. 277:28,601–28,608.

    CAS  Google Scholar 

  202. Kojima, F., Naraba, H., Sasaki, Y., Okamoto, R., Koshino, T., and Kawai, S. (2002). Coexpression of microsomal prostaglandin E synthase with cyclooxygenase-2 in human rheumatoid synovial cells. J. Rheumatol. 29:1836–1842.

    PubMed  CAS  Google Scholar 

  203. Soler, M., Camacho, M., Escudero, J.R., Iniguez, M.A., and Vila, L. (2000). Human vascular smooth muscle cells but not endothelial cells express prostaglandin E synthase. Circ. Res. 87:504–507.

    PubMed  CAS  Google Scholar 

  204. Matsumoto, H., Naraba, H., Murakami, M., Kudo, I., Yamaki, K., Ueno, A., and Oh-ishi, S. (1997). Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophages. Biochem. Biophys. Res. Commun. 230:110–114.

    PubMed  CAS  Google Scholar 

  205. Coleman, R.A., Smith, W.L., and Narumiya, S. (1994). International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol. Rev. 46:205–229.

    PubMed  CAS  Google Scholar 

  206. Libby, P., Warner, S.J., and Friedman, G.B. (1988). Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J. Clin. Invest. 81:487–498.

    PubMed  CAS  Google Scholar 

  207. Corcoran, M.L., Stetler-Stevenson, W.G., DeWitt, D.L., and Wahl, L.M. (1994). Effect of cholera toxin and pertussis toxin on prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinase production by human monocytes. Arch. Biochem. Biophys. 310:481–488.

    PubMed  CAS  Google Scholar 

  208. Cipollone, F., Fazia, M., Iezzi, A., Ciabattoni, G., Pini, B., Cuccurullo, C., et al. (2004). Balance between PGD synthase and PGE synthase is a major determinant of atherosclerotic plaque instability in humans. Arterioscler. Thromb Vasc. Biol. 24:1259–1265.

    PubMed  CAS  Google Scholar 

  209. Callejas, N.A., Casado, M., Diaz-Guerra, M.J., Bosca, L., and Martin-Sanz, P. (2001). Expression of cyclooxygenase-2 promotes the release of matrix metalloproteinase-2 and-9 in fetal rat hepatocytes. Hepatology 33:860–867.

    PubMed  CAS  Google Scholar 

  210. Shankavaram, U.T., Lai, W.C., Netzel-Arnett, S., Mangan, P.R., Ardans, J.A., Caterina, N., et al. (2001). Monocyte membrane type 1-matrix metalloproteinase. Prostaglandin-dependent regulation and role in metalloproteinase-2 activation. J. Biol. Chem. 276:19027–19032.

    PubMed  CAS  Google Scholar 

  211. Wesley, R.B. 2nd, Meng, X., Godin, D., and Galis, Z.S. (1998). Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro. Arterioscler. Thromb. Vasc. Biol. 18:432–440.

    PubMed  CAS  Google Scholar 

  212. Hinson, R.M., Williams, J.A., and Shacter, E. (1996). Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2. Proc. Natl. Acad. Sci. USA 93:4885–4890.

    PubMed  CAS  Google Scholar 

  213. Takayama, K., Garcia-Cardena, G., Sukhova, G.K., Comander, J., Gimbrone, M.A. Jr., and Libby, P. (2002). Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor. J. Biol. Chem. 277:44,147–44,154.

    CAS  Google Scholar 

  214. Haugen, G. and Helland, I. (2001). Influence of preeclampsia or maternal intake of omega-3 fatty acids on the vasoactive effect of prostaglandin F-two-alpha in human umbilical arteries. Gynecol. Obstet. Invest. 52:75–81.

    PubMed  CAS  Google Scholar 

  215. Palea, S., Toson, G., Pietra, C., Trist, D.G., Artibani, W., Romano, O., et al. (1998). Pharmacological characterization of thromboxane and prostanoid receptors in human isolated urinary bladder. Br. J. Pharmacol. 124:865–872.

    PubMed  CAS  Google Scholar 

  216. Peri, K.G., Quiniou, C., Hou, X., Abran, D., Varma, D.R., Lubell, W.D., et al. (2002). THG113: a novel selective FP antagonist that delays preterm labor. Semin. Perinatol. 26:389–397.

    PubMed  Google Scholar 

  217. Stier, C.T., Jr., Roberts, L.J. 2nd, and Wong, P.Y. (1987). Renal response to 9 alpha, 11 beta-prostaglandin F2 in the rat. J. Pharmacol. Exp. Ther. 243:487–491.

    PubMed  CAS  Google Scholar 

  218. Honda, K., Arima, M., Cheng, G., Taki, S., Hirata, H., Eda, F., et al. (2003). Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine. J. Exp. Med. 198:533–543.

    PubMed  CAS  Google Scholar 

  219. Arimura, A., Yasui, K., Kishino, J., Asanuma, F., Hasegawa, H., Kakudo, S., et al. (2001). Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. J. Pharmacol. Exp. Ther. 298:411–419.

    PubMed  CAS  Google Scholar 

  220. Fujitani, Y., Kanaoka, Y., Aritake, K., Uodome, N., Okazaki-Hatake, K., and Urade, Y. (2002). Prononuced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice. J. Immunol. 168:443–449.

    PubMed  CAS  Google Scholar 

  221. Minami, T., Okuda-Ashitaka, E., Nishizawa, M., Mori, H., and Ito, S. (1997). Inhibition of nociceptin-induced allodynia in conscious mice by prostaglandin D2. Br. J. Pharmacol. 122:605–610.

    PubMed  CAS  Google Scholar 

  222. VanderEnde, D.S. and Morrow, J.D. (2001). Release of markedly increased quantities of prostaglandin D2 from the skin in vivo in humans after the application of cinnamic aldehyde. J. Am. Acad. Dermatol. 45:62–67.

    PubMed  CAS  Google Scholar 

  223. Walch, L., Labat, C., Gascard, J.P., de Montpreville, V., Brink, C., and Norel, X. (1999). Prostanoid receptors involved in the relaxation of human pulmonary vessels. Br. J. Pharmacol. 126:859–866.

    PubMed  CAS  Google Scholar 

  224. Cooper, B. (1979). Diminished platelet adenylate cyclase activation by prostaglandin D2 in acute thrombosis. Blood 54: 684–693.

    PubMed  CAS  Google Scholar 

  225. Eguchi, Y., Eguchi, N., Oda, H., Seiki, K., Kijima, Y., Matsu-ura, Y., et al. (1997). Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients. Proc. Natl. Acad. Sci. USA 94:14,689–14,694.

    CAS  Google Scholar 

  226. Garcia-Fernandez, L.F., Iniguez, M.A., Eguchi, N., Fresno, M., Urade, Y., and Munoz, A. (2000). Dexamethasone induces lipocalin-type prostaglandin D synthase gene expression in mouse neuronal cells. J. Neurochem. 75:460–470.

    PubMed  CAS  Google Scholar 

  227. Straus, D.S., Pascual, G., Li, M., Welch, J.S., Ricote, M., Hsiang, C.H., et al. (2000). 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B sig-naling pathway. Proc. Natl. Acad. Sci. USA 97:4844–4849.

    PubMed  CAS  Google Scholar 

  228. Rossi, A., Kapahi, A.C., Willson, T.M., Kelly, C.J., and Glass, C.K. (1998). The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82.

    Google Scholar 

  229. Zhao, L. and Funk, C.D. (2004). Lipoxygenase pathways in atherogenesis. Trends Cardiovasc. Med. 14:191–195.

    PubMed  CAS  Google Scholar 

  230. Spanbroek, R., Grabner, R., Lotzer, K., Hildner, M., Urbach, A., Ruhling, K., et al. (2003). Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc. Natl. Acad. Sci. USA 100:1238–1243.

    PubMed  CAS  Google Scholar 

  231. Romano, M., Catalano, A., Nutini, M., D'Urbano, E., Crescenzi, C., Claria, J., et al. (2001). 5-lipoxygenase regulates malignant mesothelial cell survival: involvement of vascular endothelial growth factor. FASEB J. 15:2326–2336.

    PubMed  CAS  Google Scholar 

  232. Celletti, F.L., Waugh, J.M., Amabile, P.G., Brendolan, A., Hilfiker, P.R., and Dake, M.D. (2001). Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat. Med. 7:425–429.

    PubMed  CAS  Google Scholar 

  233. Mehrabian, M., Allayee, H., Wong, J., Shi, W., Wang, X.P., Shaposhnik, Z., et al. (2002). Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ. Res. 91:120–126.

    PubMed  CAS  Google Scholar 

  234. Sala, A., Testa, T., and Folco, G. (1996). Leukotriene A4, and not leukotriene B4, is the main 5-lipoxygenase metabolite released by bovine leukocytes. FEBS Lett. 388:94–98.

    PubMed  CAS  Google Scholar 

  235. Sala, A., Bolla, M., Zarini, S., Muller-Peddinghaus, R., and Folco, G. (1996). Release of leukotriene A4 versus leukotriene B4 from human polymorphonuclear leukocytes. J. Biol. Chem. 271:17,944–17,948.

    CAS  Google Scholar 

  236. Maclouf, J., Murphy, R.C., and Henson, P.M. (1989). Transcellular sulfidopeptide leukotriene biosynthetic capacity of vascular cells. Blood 74:703–707.

    PubMed  CAS  Google Scholar 

  237. Yokomizo, T., Izumi, T., and Shimizu, T. (2001). Leukotriene B4: metabolism and signal transduction. Arch. Biochem. Biophys. 385:231–241.

    PubMed  CAS  Google Scholar 

  238. Friedrich, E.B., Tager, A.M., Liu, E., Pettersson, A., Owman, C., Munn, L., et al. (2003). Mechanisms of leukotriene B4—triggered monocyte adhesion. Arterioscler. Thromb. Vasc. Biol. 23:1761–1767.

    PubMed  CAS  Google Scholar 

  239. McIntyre, T.M., Zimmerman, G.A., and Prescott, S.M. (1986). Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils. Proc. Natl. Acad. Sci. USA 83:2204–2208.

    PubMed  CAS  Google Scholar 

  240. Lehr, H.A., Hubner, C., Finckh, B., Angermuller, S., Nolte, D., Beisiegel, U., et al. (1991). Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters. J. Clin. Invest. 88:9–14.

    PubMed  CAS  Google Scholar 

  241. Datta, Y.H., Romano, M., Jacobson, B.C., Golan, D.E., Serhan, C.N., and Ewenstein, B.M. (1995). Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin, surface expression in human umbilical vein endothelial cells. Circulation 92:3304–3311.

    PubMed  CAS  Google Scholar 

  242. Aiello, R.J., Bourassa, P.A., Lindsey, S., Weng, W., Freeman, A., and Showell, H.J. (2002). Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler. Thromb. Vasc. Biol. 22:443–449.

    PubMed  CAS  Google Scholar 

  243. Porreca, E., Conti, P., Feliciani, C., Di Febbo, C., Reale, M., Mincione, G., et al. (1995). Cysteinyl-leukotriene D4 induced IL-1 beta expression and release in rat vascular smooth muscle cells. Atherosclerosis 115:181–189.

    PubMed  CAS  Google Scholar 

  244. Devaraj, S. and Jialal I. (1999). Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler. Thromb. Vasc. Biol. 19:1125–1133.

    PubMed  CAS  Google Scholar 

  245. Porreca, E., Di Sciullo, A., Angelucci D., Nasuti, M., Vitullo, P., et al. (1996). Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia. Thromb. Haemost. 76:99–104.

    PubMed  CAS  Google Scholar 

  246. Nigam, S. and Schewe, T. (2000). Phospholipase A(2)s and lipid peroxidation. Biochim. Biophys. Acta 1488: 167–181.

    PubMed  CAS  Google Scholar 

  247. Kuwata, H., Yamamoto, S., Takekura, A., Murakami, M., and Kudo, I. (2004). Group IIA secretory phospholipase A2 is a unique 12/15-lipoxygenase-regulated gene in cytokine-stimulated rat fibroblastic 3Y1 cells. Biochim. Biophys. Acta 1686:15–23.

    PubMed  CAS  Google Scholar 

  248. Huo, Y., Zhao, L., Hyman, M.C., Shashkin, P., Harry, B.L., Burcin, T., et al. (2004). Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation 110:2024–2031.

    PubMed  CAS  Google Scholar 

  249. George, J., Afek, A., Shaish, A., Levkovitz, H., Bloom, N., Cyrus, T., et al. (2001). 12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice. Circulation 104:1646–1650.

    PubMed  CAS  Google Scholar 

  250. Kume, N., Cybulsky, M.I., and Gimbrone, M.A. Jr. (1992). Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J. Clin. Invest. 90:1138–1144.

    PubMed  CAS  Google Scholar 

  251. Murohara, T., Kugiyama, K., Ohgushi, M., Sugiyama, S., Ohta, Y., and Yasue, H. (1994). LPC in oxidized LDL elicits vasocontraction and inhibits endothelium-dependent relaxation. Am. J. Physiol. 267:H2441-H2449.

    PubMed  CAS  Google Scholar 

  252. Chai, Y.C., Howe, P.H., DiCorleto, P.E., and Chisolm, G.M. (1996). Oxidized low density lipoprotein and lysophosphatidylcholine stimulated cell cycle entry invascular smooth muscle cells. Evidence for release of fibroblast growth factor-2. J. Biol. Chem. 271:17,791–17,797.

    CAS  Google Scholar 

  253. Lauber, K., Bohn, E., Krober, S.M., Xiao, Y.J., Blumenthal, S.G., Lindemann, R.K., et al. (2003). Apoptotic cells induced migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717–730.

    PubMed  CAS  Google Scholar 

  254. McMurray, H.F., Parthasarathy, S., and Steinberg, D. (1993). Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J. Clin. Invest. 92:1004–1008.

    PubMed  CAS  Google Scholar 

  255. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (19809). Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 320:915–924.

    Google Scholar 

  256. Steinbrecher, U.P., Parthasarathy, S., Leake, D.S., Witztum, J.L., and Steinberg, D. (1984). Modification of low density liprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc. Natl. Acad. Sci. USA 81:3883–3887.

    PubMed  CAS  Google Scholar 

  257. Keaney, J.F. Jr., Xu, A., Cunningham, D., Jackson, T., Frei, B., and Vita, J.A. (1995). Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J. Clin. Invest. 95:2520–2529.

    PubMed  CAS  Google Scholar 

  258. Portman, O.W. and Alexander, M. (1969). Lysophosphatidylcholine concentrations and metabolism in aortic intima plus inner media: effect of nutritionally induced atherosclerosis. J. Lipid Res. 10:158–165.

    PubMed  CAS  Google Scholar 

  259. Liu-Wu, Y., Hurt-Camejo, E., and Wiklund, O. (1998). Lysophosphatidylcholine induces the production of IL-1 beta by human monocytes. Atherosclerosis 137:351–357.

    PubMed  CAS  Google Scholar 

  260. Pages, C., Simon, M.F., Valet, P., and Saulnier-Blache, J.S. (2001). Lysophosphatidic acid synthesis and release. Prostaglandins Other Lipid Mediat. 64:1–10.

    PubMed  CAS  Google Scholar 

  261. Xie, Y. and Meier K.E. (2004). Lysophospholipase D and its role in LPA production. Cell Signal. 16:975–981.

    PubMed  CAS  Google Scholar 

  262. Ishii, I., Fukushima, N., Ye, X., and Chun, J. (2004). Lysophospholipid receptors: signaling and biology. Annu. Rev. Biochem. 73:321–354.

    PubMed  CAS  Google Scholar 

  263. Fukushima, N., Ishii, I., Contos, J.J., Weiner, J.A., and Chun, J. (2001). Lysophospholipid receptors. Annu. Rev. Pharmacol. Toxicol. 41:507–534.

    PubMed  CAS  Google Scholar 

  264. Anliker, B. Chun, J. (2004). Cell surface receptors in lysophospholipid signaling. Semin. Cell Dev. Biol. 15:457–465.

    PubMed  CAS  Google Scholar 

  265. Guyton, J.R. (2001). Phospholipid hydrolytic enzymes in a ‘cesspool’ of arterial initimal lipoproteins: a mechanism for atherogenic lipid accumulation. Arterioscler. Thromb. Vasc. Biol. 21:884–886.

    PubMed  CAS  Google Scholar 

  266. Tabas, I. (1999). Nonxidative modifications of lipoproteins in atherogenesis. Annu. Rev. Nutr. 19:123–139.

    PubMed  CAS  Google Scholar 

  267. Oorni, K., Pentikainen, M.O., Ala-Korpela, M., and Kovanen, P.T. (2000). Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions. J. Lipid Res. 41:1703–1714.

    PubMed  CAS  Google Scholar 

  268. Khoo, J.C., Miller, E., McLoughlin, P., Steinberg, D. (1988). Enhanced macrophage uptake of low density lipoprotein after self-aggregation. Arteriosclerosis 8:348–358.

    PubMed  CAS  Google Scholar 

  269. Suits, A.G., Chait, A., Aviram, M., and Heinecke, J.W. (1989). Phagocytosis of aggregated lipoprotein by macrophages: low density liproprotein receptor-dependent foam-cell formation. Proc. Natl. Acad. Sci USA 86:2713–2717.

    PubMed  CAS  Google Scholar 

  270. Oorni, K., Hakala, J.K., Annila, A., Ala-Korpela, M., and Kovanen, P.T. (1998). Sphingomyelinase induces aggregation and fusion, but phospholipase A2 only aggregation, of low density lipoprotein (LDL) particles. Two distinct mechanisms leading to increased binding strength of LDL to human aortic proteoglycans. J. Biol. Chem. 273:29,127–29,134.

    CAS  Google Scholar 

  271. Kleinman, Y., Krul, E.S., Burnes, M., Aronson, W., Pfleger, B., and Schonfeld, G. (1988). Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J. Lipid Res. 29:729–743.

    PubMed  CAS  Google Scholar 

  272. Gorshkova, I.N., Menschikowski, M., and Jaross, W. (1996). Alterations in the physiochemical characteristics of low and high density lipoproteins after lipolysis with phospholipase A2. A spin-label study. Biochim. Biophys. Acta 1300:1103–113.

    Google Scholar 

  273. Hurt-Camejo, E., Andersen, S., Standal, R., Rosengren, B., Sartipy, P., Stadberg, E., et al. (1997). Localization of nonpancreatic secretory phospholipase A2 in normal and atherosclerotic arteries. Activity of the isolated enzyme on low-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 17:300–309.

    PubMed  CAS  Google Scholar 

  274. Camejo, G., Hurt, E., Wiklund, O., Rosengren, B., Lopez, F., and Bondjers, G. (1991). Modification of low-density lipoprotein induced by arterial proteoglycans and chondroitin-6-sulfate. Biochim. Biophys. Acta 1096:253–261.

    PubMed  CAS  Google Scholar 

  275. Mateu, L., Avila, E.M., Camejo, G., Leon, V., and Liscano, N. (1984). The structural stability of low-density lipoprotein. A kinetic X-ray scattering study of its interaction with arterial proteoglycans. Biochim. Biophys. Acta 795:525–534.

    PubMed  CAS  Google Scholar 

  276. Pentikainen, M.O., Oorni, K., Lassila, R., and Kovanen, P.T. (1997). The proteoglycandecorin links low density lipoproteins with collagen type I. J. Biol. Chem. 272:7633–7638.

    PubMed  CAS  Google Scholar 

  277. Han, S.K., Yoon, E.T., and Cho, W. (1988). Bacterial expression and characterization of human secretory class V phospholipase A2. Biochem. J. 331 (Pt. 2):353–357.

    Google Scholar 

  278. Riessen, R., Isner, J.M., Blessing, E., Loushin, C., Nikol, S., and Wight, T.N. (1994). Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries. Am. J. Pathol. 144:962–974.

    PubMed  CAS  Google Scholar 

  279. Austin, M.A., King, M.C., Vranizan, K.M., Newman, B., and Krauss, R.M. (1988). Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis. Am. J. Hum. Genet. 43:838–846.

    PubMed  CAS  Google Scholar 

  280. Schissel, S.L., Tweedie-Hardman, J., Rapp, J.H., Graham, G., Williams, S.L., Tweedie-Hardman, J., Rapp, J.H., Graham, G., Williams, K.J., and Tabas, I. (1996). Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J. Clin. Invest. 98:1455–1464.

    PubMed  CAS  Google Scholar 

  281. Schissel, S.L., Jiang, X., Tweedie-Hardman, J., Jeong, T., Camejo, E.H., Najib, J., et al. (1998). Secretory sphingomyelinase, a product of the acid sphingomyelinase gene, can hydrolyze atherogenic lipoproteins, at neutral pH. Implications for atherosclerotic lesions development. J. Biol. Chem. 273:2738–2746.

    PubMed  CAS  Google Scholar 

  282. Pentikainen, M.O., Lehtonen, E.M., and Kovanen, P.T. (1996). Aggregation and fusion of modified low density lipoprotein. J. Lipid. Res. 37:2638–2649.

    PubMed  CAS  Google Scholar 

  283. Xu, X.X. and Tabas, I. (1991). Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesterylester accumulation in macrophage. J. Biol. Chem. 266:24,849–24,858.

    CAS  Google Scholar 

  284. Dziennis, S., Van Etten, R.A., Pahl, H.L., Morris, D.L., Rothstein, T.L., Blosch, C.M., et al. (1995). The CD11b promoter directs high-level expresion of reporter genes in macrophage in transgenic mice. Blood 85:319–329.

    PubMed  CAS  Google Scholar 

  285. Gilroy, D.W., Newson, J., Sawmynaden, P., Willoughby, D.A., and Croxtall, J.D. (2004). A novel role for phospholipase A2 isoforms in the checkpoint control of acute inflammation. FASEB J. 18:489–498.

    PubMed  CAS  Google Scholar 

  286. Levy, B.D., Clish, C.B., Schmidt, B., Gronert, K., and Serhan, C.N. (2001). Lipid mediator class witching during acute inflammation: signals in resolution. Nat. Immunol. 2:612–619.

    PubMed  CAS  Google Scholar 

  287. Gilroy, D.W., Colville-Nash, P.R., Willis, D., Chivers, J., Paul-Clark, M.J., and Willoughby, D.A. (1999). Inducible cyclooxygenase may have anti-inflammatory properties. Nat. Med. 5:698–701.

    PubMed  CAS  Google Scholar 

  288. Steed, D.L. (2003). Wound-healing trajectories. Surg. Clin. North Am. 83:547–555, vi–vii.

    PubMed  Google Scholar 

  289. Harwig, S.S., Tan, L., Qu, X.D., Cho, Y., Eisenhauer, P.B., and Lehrer, R.I. (1995). Bactericidal properties of murine intestinal phospholipase A2. J. Clin. Invest. 95:603–610.

    PubMed  CAS  Google Scholar 

  290. Buckland, A.G., Heeley, E.L., and Wilton, D.C. (2000). Bacterial cell membrane hydrolysis by secreted phospholipases A(2): a major physiological role of human group IIa sPLA(2) involving both bacterial cell wall penetration and interfacial catalysis. Biochim. Biophys. Acta 1484:195–206.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, UNS50/11, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands

    Stijn A. I. Ghesquiere, Marten H. Hofker & Menno P. J. de Winther

Authors
  1. Stijn A. I. Ghesquiere
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marten H. Hofker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Menno P. J. de Winther
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Menno P. J. de Winther.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghesquiere, S.A.I., Hofker, M.H. & de Winther, M.P.J. The role of phospholipases in lipid modification and atherosclerosis. Cardiovasc Toxicol 5, 161–182 (2005). https://doi.org/10.1385/CT:5:2:161

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/CT:5:2:161

Key Words

Search

Navigation