title: Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis.
abstract: Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans.
authors.affiliation: The University of Chicago, Department of Pathology, Chicago, IL, USA.
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
references.citation: Semin Immunopathol. 2009 Jun;31(1):5-22
references.pmid: 19449008
references.citation: J Lipid Res. 2000 Sep;41(9):1495-508
references.pmid: 10974057
references.citation: Clin Exp Pharmacol Physiol. 2010 Jul;37(7):719-25
references.pmid: 20374263
references.citation: Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H866-73
references.pmid: 19561306
references.citation: J Lipid Res. 2008 Jun;49(6):1344-52
references.pmid: 18323573
references.citation: J Lipid Res. 2001 Jul;42(7):1096-104
references.pmid: 11441137
references.citation: Atherosclerosis. 2010 Aug;211(2):361-70
references.pmid: 20138281
references.citation: J Lipid Res. 2011 Feb;52(2):361-73
references.pmid: 21068008
references.citation: Circulation. 1999 Oct 26;100(17):1816-22
references.pmid: 10534470
references.citation: Circulation. 1989 Jan;79(1):8-15
references.pmid: 2642759
references.citation: J Lipid Res. 1988 Mar;29(3):245-71
references.pmid: 3288703
references.citation: Nat Rev Cardiol. 2011 May;8(5):266-77
references.pmid: 21243009
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):12-22
references.pmid: 14604830
references.citation: J Lipid Res. 2011 Mar;52(3):435-50
references.pmid: 21159667
references.citation: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):139-43
references.pmid: 19797709
references.citation: Circulation. 2004 Jun 29;109(25):3215-20
references.pmid: 15197147
references.citation: J Intern Med. 2008 May;263(5):479-88
references.pmid: 18410591
references.citation: J Am Coll Cardiol. 2008 Jun 10;51(23):2199-211
references.pmid: 18534265
references.citation: Drug Metab Lett. 2010 Aug;4(3):139-48
references.pmid: 20642447
references.citation: J Lipid Res. 2011 Jun;52(6):1200-1210
references.pmid: 21444758
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12040-4
references.pmid: 8265667
references.citation: Curr Drug Targets. 2007 Dec;8(12):1297-306
references.pmid: 18220706
references.citation: J Biol Chem. 1985 Aug 25;260(18):10248-55
references.pmid: 4019510
references.citation: Arthritis Res Ther. 2010;12(3):R93
references.pmid: 20482780
references.citation: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):246-52
references.pmid: 19965776
references.citation: N Engl J Med. 2006 Mar 23;354(12):1264-72
references.pmid: 16554528
references.citation: J Biol Chem. 2009 Nov 20;284(47):32336-43
references.pmid: 19783654
references.citation: Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):242-9
references.pmid: 16373607
references.citation: Arterioscler Thromb Vasc Biol. 2010 May;30(5):946-52
references.pmid: 20167655
references.citation: Cardiol Rev. 2010 May-Jun;18(3):141-7
references.pmid: 20395699
references.citation: Cell Metab. 2010 Feb 3;11(2):125-35
references.pmid: 20142100
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1325-31
references.pmid: 15831812
references.citation: J Lipid Res. 2007 Sep;48(9):1915-23
references.pmid: 17570869
references.citation: Circulation. 2002 Jan 22;105(3):290-2
references.pmid: 11804981
references.citation: J Intern Med. 2008 Dec;264(6):563-70
references.pmid: 18783480
references.citation: Nat Cell Biol. 2003 Sep;5(9):781-92
references.pmid: 12907943
references.citation: FASEB J. 2011 Jan;25(1):290-300
references.pmid: 20876212
references.citation: J Lipid Res. 2006 Jan;47(1):107-14
references.pmid: 16210729
references.citation: Am J Physiol Cell Physiol. 2010 Jun;298(6):C1538-48
references.pmid: 20219948
references.citation: J Biol Chem. 2004 Jun 18;279(25):26509-17
references.pmid: 15075321
references.citation: Am J Cardiol. 1998 Nov 26;82(10B):30T-36T
references.pmid: 9860371
references.citation: Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1642-8
references.pmid: 20466975
references.citation: J Proteome Res. 2010 Oct 1;9(10):5239-49
references.pmid: 20718489
references.citation: Circulation. 2001 Nov 13;104(20):2447-52
references.pmid: 11705823
references.citation: J Biol Chem. 2003 Mar 14;278(11):9142-9
references.pmid: 12511559
references.citation: Nat Rev Immunol. 2010 Jan;10(1):36-46
references.pmid: 19960040
references.citation: J Clin Invest. 1991 Dec;88(6):2039-46
references.pmid: 1752961
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S172-7
references.pmid: 19020338
references.citation: J Lipid Res. 2004 Jun;45(6):993-1007
references.pmid: 15060092
references.citation: Curr Drug Targets. 2007 Dec;8(12):1239-48
references.pmid: 18220701
references.citation: Annu Rev Biochem. 1977;46:897-930
references.pmid: 197883
references.citation: Curr Opin Lipidol. 2000 Apr;11(2):117-22
references.pmid: 10787172
references.citation: Proc Natl Acad Sci U S A. 1979 Jan;76(1):333-7
references.pmid: 218198
references.citation: J Biol Chem. 1995 Jan 27;270(4):1602-11
references.pmid: 7829491
references.citation: Curr Opin Investig Drugs. 2008 Nov;9(11):1157-62
references.pmid: 18951294
references.citation: Nat Med. 2003 Jun;9(6):736-43
references.pmid: 12740573
references.citation: Circulation. 2008 Mar 4;117(9):1216-27
references.pmid: 18316498
references.citation: World J Gastroenterol. 2010 Dec 21;16(47):5908-15
references.pmid: 21157966
references.citation: Circulation. 2003 May 13;107(18):2337-41
references.pmid: 12732610
references.citation: J Lipid Res. 2008 Nov;49(11):2302-11
references.pmid: 18621920
references.citation: J Lipid Res. 2008 Jun;49(6):1268-83
references.pmid: 18323574
references.citation: Biochemistry. 1995 Jun 20;34(24):7955-65
references.pmid: 7794908
references.citation: J Am Coll Cardiol. 2007 Aug 7;50(6):540-6
references.pmid: 17678738
references.citation: Physiol Rev. 2011 Jan;91(1):327-87
references.pmid: 21248169
references.citation: Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1773-8
references.pmid: 20702809
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11779-84
references.pmid: 15280540
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9607-11
references.pmid: 7937814
references.citation: Circ Res. 2005 Nov 25;97(11):1190-7
references.pmid: 16224061
references.citation: Clin Immunol. 2008 May;127(2):234-44
references.pmid: 18337176
references.citation: Circulation. 2008 Oct 28;118(18):1837-47
references.pmid: 18852364
references.citation: Nat Immunol. 2011 Mar;12(3):204-12
references.pmid: 21321594
references.citation: Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1542-8
references.pmid: 18483405
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1426-32
references.pmid: 15845909
references.citation: Subcell Biochem. 2010;51:229-51
references.pmid: 20213546
references.citation: Curr Drug Targets. 2008 Mar;9(3):196-203
references.pmid: 18336237
references.citation: Curr Pharm Des. 2010;16(28):3173-84
references.pmid: 20687877
references.citation: Circulation. 2003 Dec 2;108(22):2751-6
references.pmid: 14638544
references.citation: Circulation. 2010 Nov 9;122(19):1919-27
references.pmid: 20974999
references.citation: Nat Rev Cardiol. 2011 Apr;8(4):222-32
references.pmid: 21304474
references.citation: J Clin Invest. 2007 Mar;117(3):746-56
references.pmid: 17332893