title: Potential to inhibit growth of atherosclerotic plaque development through modulation of macrophage neopterin/7,8-dihydroneopterin synthesis.
abstract: The rise in plasma neopterin observed with increasing severity of vascular disease is a strong indicator of the inflammatory nature of atherosclerosis. Plasma neopterin originates as the oxidation product of 7,8-dihydroneopterin secreted by gamma-interferon stimulated macrophages within atherosclerotic plaques. Neopterin is increasingly being used as a marker of inflammation during clinical management of patients with a range of disorders including atherosclerosis. Yet the role of 7,8-dihydroneopterin/neopterin synthesis during the inflammatory process and plaque formation remains poorly understood and controversial. This is partially due to the unresolved role oxidants play in atherosclerosis and the opposing roles of 7,8-dihydroneopterin/neopterin. Neopterin can act as pro-oxidant, enhancing oxidant damage and triggering apoptosis in a number of different cell types. Neopterin appears to have some cellular signalling properties as well as being able to chelate and enhance the reactivity of transition metal ions during Fenton reactions. In contrast, 7,8-dihydroneopterin is also a radical scavenger, reacting with and neutralizing a range of reactive oxygen species including hypochlorite, nitric oxide and peroxyl radicals, thus protecting lipoproteins and various cell types including macrophages. This has led to the suggestion that 7,8-dihydroneopterin is synthesized to protect macrophages from the oxidants released during inflammation. The oxidant/antioxidant activity observed in vitro appears to be determined both by the relative concentration of these compounds and the specific chemistry of the in vitro system under study. How these activities might influence or modulate the development of atherosclerotic plaque in vivo will be explored in this review.
authors: School of Biological Sciences, University of Canterbury, Christchurch, New Zealand. Steven.Gieseg@canterbury.ac.nz
authors: S P
authors: SP
authors: Gieseg
authors: E M
authors: EM
authors: Crone
authors: E A
authors: EA
authors: Flavall
authors: Z
authors: Z
authors: Amit
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D019798:Neopterin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D016877:Oxidants; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C000976:7,8-dihydroneopterin; D019798:Neopterin; D002118:Calcium
references: Cancer Res. 1991 Dec 1;51(23 Pt 1):6250-3
references: 1933885
references: J Immunol. 1987 Nov 15;139(10):3474-83
references: 2824608
references: Eur Heart J. 1993 Dec;14 Suppl K:94-7
references: 8131797
references: Arterioscler Thromb Vasc Biol. 2004 May;24(5):949-54
references: 15001454
references: Biochim Biophys Acta. 2002 Aug 19;1591(1-3):139-145
references: 12183064
references: Clin Chem Lab Med. 2000 Apr;38(4):345-53
references: 10928656
references: J Leukoc Biol. 2002 Dec;72(6):1148-53
references: 12488496
references: Clin Exp Immunol. 2003 Feb;131(2):264-7
references: 12562386
references: Biochem Biophys Res Commun. 1997 May 29;234(3):774-8
references: 9175792
references: Oncogene. 1996 Nov 21;13(10):2281-5
references: 8950996
references: Free Radic Res. 2003 Sep;37(9):983-91
references: 14670006
references: Heart. 2000 Mar;83(3):346-50
references: 10677418
references: FEBS Lett. 1993 Mar 8;318(3):249-52
references: 8440379
references: Eur J Cell Biol. 2002 Apr;81(4):197-202
references: 12018387
references: Atherosclerosis. 2006 Aug;187(2):238-50
references: 16412446
references: J Biol Chem. 1994 May 20;269(20):14457-64
references: 7514170
references: J Lipid Res. 1997 May;38(5):992-1001
references: 9186916
references: Free Radic Biol Med. 2005 Jun 15;38(12):1571-84
references: 15917186
references: Atherosclerosis. 1992 May;94(1):87-8
references: 1632862
references: Immunobiology. 1998 Jul;199(1):63-73
references: 9717668
references: Arch Biochem Biophys. 1994 Apr;310(1):60-3
references: 8161222
references: Lung. 1984;162(6):337-46
references: 6527565
references: J Leukoc Biol. 1996 Apr;59(4):555-61
references: 8613704
references: Neurochem Int. 2002 Jul;41(1):71-8
references: 11918974
references: Biochim Biophys Acta. 2005 Sep 30;1745(3):361-9
references: 16084608
references: Biochem Biophys Res Commun. 2000 Aug 28;275(2):307-11
references: 10964663
references: Redox Rep. 2000;5(2-3):98-100
references: 10939282
references: J Am Coll Cardiol. 1997 Sep;30(3):703-7
references: 9283529
references: Immunobiology. 2000 Jan;201(3-4):478-91
references: 10776802
references: Biochem J. 1992 Dec 1;288 ( Pt 2):341-4
references: 1463440
references: Biochim Biophys Acta. 2004 Apr 7;1672(1):46-50
references: 15056492
references: Clin Chim Acta. 1991 Sep 14;201(1-2):1-16
references: 1790613
references: J Am Coll Cardiol. 2000 Mar 15;35(4):956-62
references: 10732894
references: Immunol Lett. 2000 May 1;72(2):133-6
references: 10841949
references: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2506-10
references: 2320571
references: Free Radic Res. 2004 Jan;38(1):9-17
references: 15061649
references: Int J Tuberc Lung Dis. 2003 Aug;7(8):771-6
references: 12921154
references: Clin Chem Lab Med. 2003 Oct;41(10):1314-9
references: 14580158
references: FEBS Lett. 1996 Nov 18;397(2-3):263-8
references: 8955360
references: Immunobiology. 2001 May;203(4):629-41
references: 11402497
references: J Lipid Res. 1997 Sep;38(9):1730-45
references: 9323583
references: J Biol Chem. 1999 Sep 10;274(37):25959-62
references: 10473535
references: J Biol Chem. 1997 Feb 7;272(6):3520-6
references: 9013599
references: Transplantation. 1983 Dec;36(6):650-3
references: 6362141
references: Clin Chim Acta. 2003 Dec;338(1-2):157-64
references: 14637281
references: Biochim Biophys Acta. 2005 Jun 20;1724(1-2):17-22
references: 15890449
references: J Biochem Biophys Methods. 1988 May;16(1):27-40
references: 3135299
references: Biochem J. 2000 Dec 15;352 Pt 3:693-9
references: 11104675
references: Biochem Biophys Res Commun. 2004 Aug 20;321(2):379-85
references: 15358187
references: Atherosclerosis. 1993 Feb;99(1):107-20
references: 8384855
references: J Infect Dis. 2006 Nov 15;194(10):1438-46
references: 17054074
references: Eur J Intern Med. 2000 Apr;11(2):89-95
references: 10745152
references: Free Radic Res. 2002 May;36(5):509-20
references: 12150539
references: Circulation. 2002 Mar 5;105(9):1135-43
references: 11877368
references: Adv Clin Chem. 1989;27:81-141
references: 2667296
references: Free Radic Res. 2007 Jul;41(7):839-48
references: 17577745
references: Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1708-18
references: 10397689
references: Free Radic Res. 2001 Feb;34(2):123-36
references: 11264890
references: Eur J Biochem. 1987 Jul 15;166(2):303-10
references: 3301338
references: J Biol Chem. 1989 Sep 15;264(26):15216-23
references: 2768257
references: Biochim Biophys Acta. 1995 May 17;1256(2):141-50
references: 7766691
references: J Pathol. 1996 Dec;180(4):423-9
references: 9014864
references: Biochem Biophys Res Commun. 1998 Jul 20;248(2):341-6
references: 9675137
references: J Clin Invest. 1994 Jul;94(1):437-44
references: 8040285
references: Clin Chem. 1992 Sep;38(9):1722-4
references: 1526005
references: Free Radic Res. 1995 Aug;23(2):123-36
references: 7581810
references: FEBS Lett. 1995 May 8;364(2):234-8
references: 7750578
references: Cardiovasc Res. 1999 Feb;41(2):334-44
references: 10341833
references: J Mol Cell Cardiol. 2000 Jul;32(7):1265-74
references: 10860768
references: Trans R Soc Trop Med Hyg. 1984;78(4):545-6
references: 6485060
references: FEBS Lett. 2001 Jun 15;499(1-2):69-72
references: 11418114
references: J Clin Invest. 1989 Oct;84(4):1086-95
references: 2794046
references: Biochem Biophys Res Commun. 1999 Oct 14;264(1):262-7
references: 10527875
references: Biochem J. 2003 Mar 1;370(Pt 2):729-35
references: 12456264
references: Clin Chem. 1987 Nov;33(11):2028-33
references: 3119253
references: Cancer Res. 1990 May 15;50(10):2863-7
references: 2110500
references: Arteriosclerosis. 1989 Jul-Aug;9(4):538-49
references: 2751482
references: Angiology. 1998 Dec;49(12):957-66
references: 9855370
references: Free Radic Biol Med. 1994 Jan;16(1):131-3
references: 7507878
references: Trends Biochem Sci. 1991 Oct;16(10):369-73
references: 1785138
references: J Clin Invest. 1994 May;93(5):2149-58
references: 8182147
references: Atherosclerosis. 1991 Aug;89(2-3):203-8
references: 1793448
references: Arthritis Rheum. 1986 Sep;29(9):1063-70
references: 3753537
references: Immunol Today. 1988 May;9(5):150-5
references: 3076770
references: Nephrol Dial Transplant. 2002 Jun;17(6):1032-6
references: 12032193
references: FEBS Lett. 1992 Jun 15;304(2-3):163-6
references: 1319924
references: Free Radic Res. 2001 Sep;35(3):311-8
references: 11697129
references: Redox Rep. 2003;8(2):113-5
references: 12804014
references: Curr Opin Lipidol. 2001 Oct;12(5):535-41
references: 11561173
references: Antioxid Redox Signal. 2001 Feb;3(1):157-63
references: 11291594
references: FEBS Lett. 1995 Jan 23;358(2):175-8
references: 7828731
references: Atherosclerosis. 1995 Nov;118(1):67-75
references: 8579633
references: Mediators Inflamm. 2002 Jun;11(3):181-5
references: 12137247
references: FEBS Lett. 1996 Aug 5;391(1-2):181-4
references: 8706912
references: J Biol Chem. 1996 Dec 20;271(51):32714-21
references: 8955104
references: Coron Artery Dis. 2006 Sep;17(6):511-6
references: 16905962
references: Proc Natl Acad Sci U S A. 1979 Jan;76(1):333-7
references: 218198
references: Redox Rep. 2003;8(2):81-6
references: 12804010
references: Metabolism. 1996 Sep;45(9):1069-79
references: 8781293
references: Biochem Pharmacol. 1998 Nov 1;56(9):1181-7
references: 9802329
references: Scand J Immunol. 1994 Jan;39(1):27-30
references: 8290891
references: J Clin Invest. 1990 Feb;85(2):554-62
references: 2153710