title: Cardiac allograft vasculopathy: a donor or recipient induced pathology?
abstract: Cardiac allograft vasculopathy (CAV) is one of the main causes of late-stage heart failure after heart transplantation. CAV is characterized by concentric luminal narrowing of the coronary arteries, but the exact pathogenesis of CAV is still not unraveled. Many researchers show evidence of an allogeneic immune response of the recipient, whereas others show contrasting results in which donor-derived cells induce an immune response against the graft. In addition, fibrosis of the neo-intima can be induced by recipient-derived circulating cells or donor-derived cells. In this review, both donor and recipient sides of the story are described to obtain better insight in the pathogenesis of CAV. Dual outcomes were found regarding the contribution of donor and recipient cells in the initiation of the immune response and the development of fibrosis during CAV. Future research could focus more on the potential synergistic interaction of donor and recipient cells leading to CAV.
authors: Department of Cardiology, Experimental Cardiology laboratory, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: Patricia
authors: P
authors: van den Hoogen
authors: Manon M H
authors: MM
authors: Huibers
authors: Joost P G
authors: JP
authors: Sluijter
authors: Roel A
authors: RA
authors: de Weger
mesh_terms: D064591:Allografts; D000818:Animals; D003324:Coronary Artery Disease / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D005355:Fibrosis; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006333:Heart Failure / Q000601:surgery*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D058426:Neointima; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome
references: Am J Pathol. 1991 Apr;138(4):791-8
references: 2012171
references: Circulation. 2008 Feb 5;117(5):660-9
references: 18212277
references: Circ Res. 2012 Jun 8;110(12):1628-45
references: 22679138
references: N Engl J Med. 2002 Jan 3;346(1):5-15
references: 11777997
references: J Am Soc Nephrol. 2007 Nov;18(11):2929-36
references: 17928506
references: Transplant Proc. 2009 Jul-Aug;41(6):2579-84
references: 19715978
references: Transplant Proc. 2006 Jun;38(5):1507-10
references: 16797344
references: J Exp Med. 1990 Jan 1;171(1):307-14
references: 2404081
references: Front Biosci. 2008;13:2980-8
references: 17981771
references: Expert Opin Pharmacother. 2006 Dec;7(17):2369-83
references: 17109612
references: Tex Heart Inst J. 2013;40(4):395-9
references: 24082367
references: J Leukoc Biol. 2001 May;69(5):705-12
references: 11358977
references: Circulation. 2005 Nov 8;112(19):2951-8
references: 16275883
references: Chest. 1996 Nov;110(5):1143-9
references: 8915211
references: J Am Soc Nephrol. 2002 Oct;13(10):2570-6
references: 12239247
references: Front Biosci. 2007;12:4362-9
references: 17485380
references: J Heart Lung Transplant. 2013 Jan;32(1):120-8
references: 23260712
references: Atherosclerosis. 2014 Oct;236(2):353-9
references: 25128973
references: Circulation. 2012 Apr 10;125(14):1795-808
references: 22492947
references: Nat Med. 2007 Aug;13(8):952-61
references: 17660828
references: Circ Heart Fail. 2009 Jul;2(4):361-9
references: 19808360
references: Lancet. 1992 Jun 27;339(8809):1579-82
references: 1351558
references: J Heart Lung Transplant. 2004 Apr;23(4):427-35
references: 15063402
references: Expert Opin Ther Targets. 2012 Aug;16(8):783-9
references: 22762198
references: J Immunol. 2007 Oct 15;179(8):5204-10
references: 17911605
references: Circulation. 2001 Dec 18;104(25):3091-6
references: 11748106
references: Clin Infect Dis. 2001 Jul 1;33 Suppl 1:S32-7
references: 11389520
references: J Cardiovasc Transl Res. 2013 Apr;6(2):263-77
references: 23135991
references: Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12145-50
references: 25092331
references: Thorax. 2009 Sep;64(9):770-7
references: 19213777
references: Transplantation. 2008 Jul 15;86(1):75-81
references: 18622281
references: Am J Transplant. 2006 May;6(5 Pt 1):986-92
references: 16611334
references: Transplantation. 2002 Oct 15;74(7):1053-7
references: 12394855
references: Transplant Proc. 2008 Oct;40(8):2609-10
references: 18929815
references: Curr Opin Organ Transplant. 2010 Feb;15(1):16-20
references: 19898237
references: J Heart Lung Transplant. 2004 May;23(5 Suppl):S187-93
references: 15093804
references: Transpl Immunol. 2011 Sep;25(2-3):124-32
references: 21782945
references: Trends Cardiovasc Med. 2005 Jan;15(1):1-8
references: 15795157
references: Circulation. 1997 Jan 7;95(1):191-6
references: 8994436
references: Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):380-7
references: 12615698
references: Cell Rep. 2012 Dec 27;2(6):1684-96
references: 23200853
references: Am J Clin Pathol. 2001 Apr;115(4):525-33
references: 11293900
references: Telemed J E Health. 2013 Apr;19(4):287-97
references: 23540278
references: Transplantation. 2003 Mar 15;75(5):679-85
references: 12640309
references: Bone Marrow Transplant. 2008 Mar;41(6):563-9
references: 18037937
references: Transplant Rev (Orlando). 2009 Apr;23(2):69-79
references: 19298938
references: Circ Res. 2006 Oct 13;99(8):801-15
references: 17038650
references: Curr Opin Organ Transplant. 2009 Oct;14(5):477-82
references: 19617825
references: Circulation. 2003 Jul 15;108(2):143-9
references: 12835206
references: Transplantation. 2003 Aug 15;76(3):609-14
references: 12923453
references: J Immunol. 2002 Aug 1;169(3):1168-74
references: 12133936
references: Fibrogenesis Tissue Repair. 2012 Jun 06;5(Suppl 1):S7
references: 23259736
references: Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1609-14
references: 24903097
references: Hum Immunol. 2010 Dec;71(12):1191-6
references: 20868717
references: Circ Res. 2009 Nov 20;105(11):1128-40
references: 19815820
references: Thorac Surg Clin. 2015;25(1):27-33
references: 25430427
references: J Cell Mol Med. 2011 Dec;15(12):2781-3
references: 21914126
references: Hum Immunol. 2013 Nov;74(11):1478-85
references: 23876679
references: J Heart Lung Transplant. 2013 Oct;32(10):951-64
references: 24054804
references: JACC Heart Fail. 2014 Feb;2(1):73-83
references: 24611131
references: N Engl J Med. 2003 Feb 13;348(7):593-600
references: 12584367
references: Curr Opin Infect Dis. 2007 Aug;20(4):425-31
references: 17609604
references: Curr Treat Options Cardiovasc Med. 2014 Jan;16(1):278
references: 24346852
references: Hepatology. 2008 Apr;47(4):1352-62
references: 18220273
references: Ann Surg. 2015 Mar;261(3):591-7
references: 25371129
references: Curr Opin Cardiol. 2000 Nov;15(6):422-9
references: 11198625
references: Curr Control Trials Cardiovasc Med. 2000;1(3):166-171
references: 11714434
references: Transplant Proc. 1999 Dec;31(8):3340-2
references: 10616499
references: J Immunol. 2006 Feb 1;176(3):1447-55
references: 16424172
references: J Am Soc Nephrol. 2003 Feb;14(2):493-9
references: 12538752
references: Am J Transplant. 2007 Dec;7(12):2675-82
references: 17924996
references: Am J Transplant. 2004 Jul;4(7):1013-8
references: 15196056
references: Cardiovasc Pathol. 2014 Sep-Oct;23(5):253-60
references: 24972526
references: J Thorac Dis. 2014 Aug;6(8):1054-62
references: 25132972
references: J Immunol. 2008 Sep 1;181(5):3212-20
references: 18713992
references: Am J Transplant. 2013 May;13(5):1217-26
references: 23621161
references: J Heart Lung Transplant. 2011 Sep;30(9):1044-50
references: 21640617
references: Curr Opin Immunol. 2002 Oct;14(5):576-83
references: 12183156
references: Trends Immunol. 2004 Dec;25(12):677-86
references: 15530839
references: J Am Soc Nephrol. 2009 Mar;20(3):535-44
references: 19129312
references: J Heart Lung Transplant. 2000 Jun;19(6):522-8
references: 10867331
references: J Clin Invest. 2014 Mar;124(3):1052-6
references: 24509079
references: Ann Surg. 1999 Apr;229(4):570-8
references: 10203092
references: Transpl Int. 2010 Jun;23(6):641-8
references: 20102553
references: J Transplant. 2013;2013:521369
references: 23691272
references: J Immunol. 2011 Jul 15;187(2):1023-30
references: 21677143
references: J Heart Lung Transplant. 2009 Feb;28(2):156-62
references: 19201341
references: Annu Rev Pathol. 2009;4:19-47
references: 18717641
references: J Heart Lung Transplant. 2012 May;31(5):459-66
references: 22418079
references: Am J Transplant. 2005 Jun;5(6):1367-74
references: 15888043
references: J Am Coll Cardiol. 2012 Mar 13;59(11):1008-16
references: 22402073
references: N Engl J Med. 2003 Aug 28;349(9):847-58
references: 12944570
references: Transplantation. 2011 May 27;91(10):1153-8
references: 21544036