title: Immune-mediated vascular injury and dysfunction in transplant arteriosclerosis.
abstract: Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure.
authors: Department of Molecular Biology and Biochemistry, Simon Fraser University , Burnaby, BC , Canada.
authors: Anna
authors: A
authors: von Rossum
authors: Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia , Vancouver, BC , Canada.
authors: Ismail
authors: I
authors: Laher
authors: Department of Molecular Biology and Biochemistry, Simon Fraser University , Burnaby, BC , Canada.
authors: Jonathan C
authors: JC
authors: Choy
keywords: T cell; antibodies; blood vessels; endothelium; organ transplantation; transplant arteriosclerosis
references: Am J Pathol. 1977 Mar;86(3):675-84
references: 842616
references: Science. 1991 Sep 6;253(5024):1129-32
references: 1653454
references: Am J Pathol. 1991 Oct;139(4):709-15
references: 1928295
references: Transplantation. 2013 Jan 27;95(2):341-6
references: 23197178
references: Nature. 2000 Jan 13;403(6766):207-11
references: 10646607
references: J Biol Chem. 2004 Jan 9;279(2):963-9
references: 14581470
references: Mod Pathol. 2003 May;16(5):460-70
references: 12748253
references: J Immunol. 2012 Jun 15;188(12):6287-99
references: 22566565
references: Am J Pathol. 2002 Oct;161(4):1485-95
references: 12368221
references: Immunol Res. 2010 Jul;47(1-3):25-44
references: 20135240
references: J Heart Lung Transplant. 2008 Dec;27(12):1333-9
references: 19059114
references: Lab Invest. 1981 Apr;44(4):301-8
references: 7206628
references: Circulation. 2008 Sep 16;118(12):1276-84
references: 18765390
references: Eur J Immunol. 2010 Mar;40(3):733-43
references: 20049875
references: Circ Heart Fail. 2009 Sep;2(5):409-16
references: 19808370
references: Am J Transplant. 2014 Aug;14(8):1765-77
references: 24984831
references: J Biol Chem. 2005 Jun 24;280(25):23549-58
references: 15843372
references: N Engl J Med. 2013 Sep 26;369(13):1215-26
references: 24066742
references: J Heart Lung Transplant. 2005 Nov;24(11):1710-20
references: 16297770
references: Front Biosci. 2007 Sep 01;12 :4932-45
references: 17569621
references: Circulation. 2004 May 11;109 (18):2168-71
references: 15123533
references: Nature. 1984 Apr 12-18;308(5960):645-7
references: 6424031
references: Annu Rev Immunol. 2010;28:367-88
references: 20192808
references: Am J Pathol. 2004 Jul;165(1):127-33
references: 15215168
references: Circulation. 2006 Oct 10;114(15):1599-607
references: 17015796
references: Hum Immunol. 2006 Aug;67(8):568-78
references: 16916652
references: FASEB J. 2004 Apr;18(6):705-7
references: 14977881
references: N Engl J Med. 2008 Jan 24;358(4):353-61
references: 18216355
references: Proc Natl Acad Sci U S A. 1989 Nov;86(21):8412-6
references: 2813399
references: J Clin Invest. 2004 Sep;114(6):846-56
references: 15372109
references: Circulation. 1993 Sep;88(3):1093-100
references: 8353871
references: Arterioscler Thromb Vasc Biol. 2011 May;31(5):1177-84
references: 21330602
references: Transpl Int. 2011 Oct;24(10):1027-39
references: 21797940
references: J Immunol. 2007 Oct 15;179(8):5246-54
references: 17911610
references: Transplantation. 1988 May;45(5):943-8
references: 3285541
references: J Immunol. 2002 Dec 15;169(12):6850-5
references: 12471117
references: Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):309-16
references: 10669625
references: Circulation. 1985 Oct;72(4):735-40
references: 3896561
references: Am J Pathol. 2000 Sep;157(3):859-65
references: 10980125
references: J Immunol. 1995 Jan 1;154(1):151-61
references: 7995934
references: Blood. 2008 Jul 15;112(2):340-9
references: 18339897
references: Clin Exp Rheumatol. 1997 Mar-Apr;15(2):163-7
references: 9196868
references: J Clin Invest. 1998 Nov 1;102(9):1682-9
references: 9802882
references: Transplantation. 2010 May 27;89(10):1189-97
references: 20220570
references: J Immunol. 2012 Feb 1;188(3):1544-50
references: 22219320
references: Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1795-801
references: 20539019
references: J Immunol. 2010 Jul 15;185(2):1283-94
references: 20562257
references: Transplantation. 1999 Mar 27;67(6):897-903
references: 10199740
references: Am J Pathol. 2006 Jun;168(6):2054-63
references: 16723718
references: Tissue Antigens. 2012 Dec;80(6):477-87
references: 23137319
references: Transplant Proc. 1973 Mar;5(1):303-5
references: 4695947
references: J Biol Chem. 2011 Apr 22;286(16):13846-51
references: 21343293
references: Am J Transplant. 2009 Jan;9(1):231-5
references: 18976298
references: Circ Res. 2011 Aug 5;109(4):418-27
references: 21700930
references: J Clin Invest. 1996 Feb 1;97(3):833-8
references: 8609241
references: J Heart Lung Transplant. 1996 Dec;15(12):1233-47
references: 8981209
references: Transplantation. 1994 May 15;57(9):1367-71
references: 7910422
references: Mol Cells. 2012 Oct;34(4):341-7
references: 22752759
references: Arteriosclerosis. 1990 Nov-Dec;10(6):1082-7
references: 2173900
references: Nat Rev Immunol. 2007 Oct;7(10):803-15
references: 17893694
references: J Exp Med. 1983 Apr 1;157(4):1339-53
references: 6403654
references: Nat Med. 1998 Dec;4(12 ):1392-6
references: 9846576
references: Transplantation. 2013 Aug 15;96(3):258-66
references: 23823649
references: Arterioscler Thromb Vasc Biol. 1998 Jan;18(1):27-32
references: 9445252
references: J Exp Med. 2008 Dec 22;205(13):3145-58
references: 19075290
references: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10480-4
references: 1720542
references: Am J Transplant. 2014 Jan;14(1):184-92
references: 24354875
references: J Immunol. 1994 May 15;152(10):5135-41
references: 8176230
references: Am J Physiol Cell Physiol. 2012 Oct 15;303(8):C872-82
references: 22914643
references: Immunity. 2014 Oct 16;41(4):529-42
references: 25367570
references: Am J Transplant. 2012 Feb;12(2):313-21
references: 22070565
references: J Immunol. 1998 Sep 1;161(5):2158-67
references: 9725207
references: J Exp Med. 2013 Feb 11;210(2):257-68
references: 23382542
references: Circulation. 2001 Dec 18;104(25):3091-6
references: 11748106
references: Am J Pathol. 1992 May;140(5):1025-30
references: 1374586
references: Circulation. 2011 Oct 25;124(17):1860-70
references: 21969008
references: J Mol Cell Cardiol. 2001 Sep;33(9):1673-90
references: 11549346
references: Transplantation. 2004 Dec 15;78(11):1634-9
references: 15591952
references: Eur J Immunol. 2007 Jan;37(1):177-92
references: 17163451
references: J Immunol. 2007 Jun 15;178(12):7911-22
references: 17548629
references: J Heart Lung Transplant. 2004 Feb;23(2):193-203
references: 14761767
references: Cardiovasc Res. 2013 Mar 15;97(4):696-704
references: 23263331
references: Am J Transplant. 2012 Aug;12(8):2029-43
references: 22845908
references: Circulation. 2001 Aug 7;104(6):653-7
references: 11489770
references: Transplantation. 2012 Feb 27;93(4):373-82
references: 22245872
references: Am J Transplant. 2013 Feb;13(2):299-311
references: 23279566
references: Circ Res. 2012 Jan 6;110(1):94-104
references: 22076637
references: Circulation. 1989 Nov;80(5 Pt 2):III122-5
references: 2805291
references: J Immunol. 2008 Feb 15;180(4):2357-66
references: 18250445
references: Am Heart J. 1998 Apr;135(4):628-33
references: 9539478
references: Nature. 1983 Oct 20-26;305(5936):726-9
references: 6415484
references: Transplantation. 2012 Feb 27;93(4):364-72
references: 22273841
references: J Immunol. 2011 Nov 1;187(9):4598-610
references: 21949025
references: Clin Transplant. 2008 Sep-Oct;22(5):609-16
references: 18459998
references: Transplant Proc. 1996 Feb;28(1):496-9
references: 8644326
references: Am J Pathol. 2007 Apr;170(4):1415-27
references: 17392180
references: Transplantation. 2009 Sep 15;88(5):653-61
references: 19741462
references: Circulation. 2013 Dec 3;128(23):2504-16
references: 24045046
references: Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2245-50
references: 15472125
references: J Heart Lung Transplant. 1992 Jan-Feb;11(1 Pt 1):24-9; discussion 30
references: 1540608
references: Am J Transplant. 2009 Nov;9(11):2607-14
references: 19843036
references: N Engl J Med. 2005 Feb 10;352(6):558-69
references: 15703421
references: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1301-6
references: 17229850
references: Pflugers Arch. 2010 May;459(6):1015-23
references: 20107832
references: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4051-6
references: 8633015
references: J Heart Lung Transplant. 2005 Oct;24(10 ):1600-5
references: 16210136
references: Circulation. 1996 Nov 1;94(9):2096-102
references: 8901657
references: J Heart Lung Transplant. 1998 May;17(5):470-8
references: 9628565
references: Nat Rev Rheumatol. 2013 Dec;9(12):731-40
references: 24189842
references: Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2057-62
references: 15374847
references: J Immunol. 2007 Nov 15;179(10):6536-46
references: 17982042
references: Am J Transplant. 2006 Jan;6(1):76-82
references: 16433759
references: Cardiovasc Toxicol. 2003;3(3):269-82
references: 14555792
references: Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):112-20
references: 18032780
references: Nat Med. 2002 Jun;8(6):582-7
references: 12042808
references: Am J Transplant. 2007 Apr;7(4):908-13
references: 17391133
references: Hum Immunol. 2004 Apr;65(4):291-302
references: 15120184
references: Transplantation. 1994 Jun 15;57(11):1628-37
references: 7912014
references: Am J Transplant. 2007 Nov;7(11):2472-82
references: 17868070
references: J Heart Lung Transplant. 2003 Sep;22(9):993-1004
references: 12957609
references: Am J Pathol. 1995 Aug;147(2):293-308
references: 7639327
references: Blood. 2004 Oct 15;104(8):2376-84
references: 15251990
references: Immunity. 2011 Nov 23;35(5):819-31
references: 22078798
references: Nat Med. 2006 Sep;12(9):1075-80
references: 16892061
references: Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2402-9
references: 21885847
references: Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11172-6
references: 1662386
references: Am J Transplant. 2005 Jun;5(6):1226-36
references: 15888026
references: Transplantation. 2001 Apr 15;71(7):886-92
references: 11349721
references: Nature. 1980 Nov 27;288(5789):373-6
references: 6253831
references: Lab Invest. 1985 Nov;53(5):513-20
references: 3903345
references: J Biol Chem. 1990 Sep 5;265(25):14705-8
references: 2118515
references: J Immunol. 2005 Oct 15;175(8):4886-96
references: 16210590
references: J Exp Med. 1991 Aug 1;174(2):493-6
references: 1713255
references: Nature. 1995 Sep 21;377(6546):239-42
references: 7545787
references: J Exp Med. 2004 Jan 19;199(2):173-83
references: 14734523
references: Circ Res. 1982 Oct;51(4):439-47
references: 7127680
references: Int Immunol. 2009 Apr;21(4):317-37
references: 19246554
references: Circ Res. 2006 Oct 13;99(8):801-15
references: 17038650
references: Am J Pathol. 1998 Jul;153(1):69-79
references: 9665467
references: FASEB J. 2006 Jul;20(9):1418-30
references: 16816117
references: Am J Transplant. 2007 Sep;7(9):2064-74
references: 17614978
references: Transplantation. 2002 Oct 15;74(7):905-12
references: 12394829
references: Nat Med. 1997 Feb;3(2):196-204
references: 9018239
references: Transplantation. 2001 Jul 27;72(2):348-50
references: 11477368
references: Transplantation. 1997 Dec 27;64(12):1838-43
references: 9422428
references: Cell. 1985 Nov;43(1):277-86
references: 2416458
references: Trends Immunol. 2012 Aug;33(8):406-12
references: 22608996
references: J Immunol. 2005 May 1;174(9):5740-9
references: 15843576
references: J Biol Chem. 2001 May 4;276(18):14924-32
references: 11279137
references: Am J Transplant. 2013 Oct;13(10):2530-9
references: 24033923
references: J Immunol. 2003 Aug 1;171(3):1526-33
references: 12874246
references: Hypertension. 2010 Feb;55(2):500-7
references: 20038749
references: J Exp Med. 2008 Dec 22;205(13):3133-44
references: 19047438
references: Nat Med. 2010 Jul;16(7):809-13
references: 20473306
references: Transplantation. 2002 Sep 27;74(6):871-6
references: 12364869
references: Circulation. 2011 Dec 13;124(24):2725-34
references: 22082680
references: Int Immunol. 2004 Aug;16(8):1055-68
references: 15226269
references: Annu Rev Immunol. 2008;26:677-704
references: 18173375
references: Circ Res. 2007 Apr 13;100(7):967-78
references: 17431198
references: J Immunol. 2004 Sep 1;173(5):3020-6
references: 15322161
references: Hum Immunol. 2000 May;61(5):518-27
references: 10773356
references: Transplantation. 1997 Dec 27;64(12):1641-5
references: 9422395
references: Am J Transplant. 2011 Nov;11(11):2405-13
references: 21942930
references: J Heart Lung Transplant. 2010 Aug;29(8):914-56
references: 20643330
references: Science. 2012 Feb 24;335(6071):984-9
references: 22323740
references: J Immunol. 2007 Oct 1;179(7):4451-63
references: 17878341
references: J Immunol. 1986 Mar 1;136(5):1680-7
references: 3485132
references: Transplantation. 2010 Jul 15;90(1):4-13
references: 20463646
references: Am J Pathol. 1990 Oct;137(4):871-82
references: 1699422
references: J Immunol. 2014 Oct 15;193(8):4010-20
references: 25217167
references: Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d
references: 21890489
references: Circ Res. 2000 May 26;86(10):1038-46
references: 10827133
references: Am J Transplant. 2005 Mar;5(3):494-9
references: 15707403
references: J Biol Chem. 1992 Jul 25;267(21):14519-22
references: 1378832
references: Crit Rev Immunol. 2008;28(3):229-48
references: 19024347
references: FASEB J. 2005 Mar;19(3):458-60
references: 15640283
references: Circulation. 1994 Jun;89(6):2768-79
references: 8205691
references: J Clin Invest. 2004 Sep;114(6):762-4
references: 15372099
references: J Exp Med. 2000 Oct 2;192(7):1015-26
references: 11015442
references: Arteriosclerosis. 1989 May-Jun;9(3):279-88
references: 2470342
references: Transplantation. 2012 Jul 15;94(1):8-13
references: 22691955
references: J Immunol. 1982 Oct;129(4):1578-83
references: 6213716
references: Cell Death Differ. 2010 Apr;17(4):567-76
references: 19876069
references: J Leukoc Biol. 2013 May;93(5):681-7
references: 23325926
references: J Heart Lung Transplant. 1998 May;17(5):487-94
references: 9628567
references: Transplantation. 2007 Nov 27;84(10):1324-34
references: 18049118
references: Curr Opin Organ Transplant. 2014 Feb;19(1):33-40
references: 24316758
references: Am J Transplant. 2012 Aug;12(8):2008-16
references: 22500984
references: J Immunol. 2004 Apr 15;172(8):4744-51
references: 15067050
references: J Biol Chem. 1996 Jul 26;271(30):18068-73
references: 8663499
references: Am J Transplant. 2014 Feb;14(2):255-71
references: 24401076
references: Circulation. 2002 Oct 29;106(18):2379-84
references: 12403670
references: Circulation. 2007 Oct 30;116(18):2062-71
references: 17938288
references: Nature. 1987 Jun 11-17;327(6122):524-6
references: 3495737
references: Transplantation. 2002 Jun 15;73(11):1757-64
references: 12084998
references: Curr Opin Organ Transplant. 2012 Aug;17(4):446-51
references: 22710387
references: Circulation. 2000 Mar 21;101(11):1303-10
references: 10725291
references: Am J Transplant. 2006 Jun;6(6):1320-30
references: 16686756
references: Nat Rev Immunol. 2003 May;3(5):361-70
references: 12766758
references: Cardiovasc Res. 2008 Sep 1;79(4):698-705
references: 18511434
references: Transpl Immunol. 1993;1(1):39-44
references: 8081761
references: Transplantation. 1992 Aug;54(2):326-32
references: 1496544
references: Cell Death Differ. 2010 Feb;17(2):291-303
references: 19730442
references: J Immunol. 2005 Aug 1;175(3):1858-66
references: 16034129
references: J Clin Invest. 1992 Sep;90(3):879-87
references: 1381725
references: J Clin Invest. 1990 Jun;85(6):2004-8
references: 2347923
references: J Clin Invest. 1994 May;93(5):2236-43
references: 7514193
references: Curr Opin Immunol. 2005 Oct;17(5):541-5
references: 16098722
references: J Heart Lung Transplant. 2006 Aug;25(8):869-79
references: 16890107
references: Transplantation. 2003 Jan 15;75(1):3-9
references: 12544863
references: J Biol Chem. 1998 Dec 11;273(50):33103-6
references: 9837872
references: J Biol Chem. 1990 Oct 5;265(28):17026-30
references: 2120210
references: J Immunol. 1994 Dec 15;153(12):5402-12
references: 7989746
references: N Engl J Med. 2003 Aug 28;349(9):847-58
references: 12944570
references: Am J Transplant. 2014 May;14(5):1142-51
references: 24684552
references: Circ Res. 2007 Sep 14;101(6):560-9
references: 17656678
references: Am J Transplant. 2012 May;12(5):1157-67
references: 22429309
references: Transplantation. 2002 Apr 15;73(7):1079-85
references: 11965035
references: Transplantation. 2004 Feb 27;77(4):538-42
references: 15084931
references: Annu Rev Immunol. 2012;30:707-31
references: 22224760
references: J Immunol. 2002 Oct 1;169(7):3581-8
references: 12244148
references: Am J Transplant. 2014 Jul;14(7):1599-611
references: 24903438
references: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1313-8
references: 17227851
references: J Immunol. 2010 May 1;184(9):5344-51
references: 20357253
references: FASEB J. 2009 Jun;23(6):1625-37
references: 19141537
references: Transpl Immunol. 2010 Feb;22(3-4):157-64
references: 19895889
references: J Heart Lung Transplant. 1999 Nov;18(11):1071-9
references: 10598730
references: Lab Invest. 1996 May;74(5):921-31
references: 8642787
references: J Leukoc Biol. 2007 Jan;81(1):1-5
references: 17032697
references: J Immunol. 1986 Sep 15;137(6):1893-6
references: 3091693