Abstract
Over the past 40 years, cardiac transplantation has evolved as the single best long-term option for eligible candidates with end-stage heart failure. Approximately 2000 transplants are performed annually in the United States, and with the institution of calcineurin-based immunotherapy, surveillance biopsies, and programmatic-based patient care, life expectancy at 1 and 12 years is 85% and 50%, respectively. Cardiac allograft vasculopathy (CAV) is the number one cause of death after the first year of transplantation. The incidence of CAV remains as high as 50% at 5 years, with life expectancy significantly abbreviated once it is recognized. Although current immunotherapy has reduced the likelihood of cellular rejection, it has not impacted CAV substantially. Better treatment of established risk factors and the advent of newer antiproliferative immunotherapy may hold promise in treating CAV. However, future therapies must address the multitude of mechanisms underlying CAV. This manuscript reviews the pathophysiology, clinical manifestations, screening, and diagnostic strategies for cardiac allograft vasculopathy while emphasizing current treatment paradigms designed to stave off or retard the progression of CAV.
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Schroeder JS, Hunt S: Cardiac transplantation. Update 1987. JAMA 1987, 258:2142–2155.
United Network for Organ Sharing: http://www.unos.org. Accessed November 15, 2005.
Eisen HJ, Tuzcu EM, Dorent R, et al.: Everolimus for the prevention of allograft rejection and vasculopathy in cardiac transplant recipients. N Engl J Med 2003, 349:847–858.
Trulock EP, Edwards LB, Taylor DO, et al.: Registry of the International Society for Heart and Lung Transplantation: Twenty-second Official Adult Lung and Heart-Lung Transplant Report—2005. J Heart Lung Transplant 2005, 24:956–967.
Bieber CP, Stinson EB, Shumway NE, et al.: Cardiac transplantation in man. VII. Cardiac allograft pathology. Circulation 1970, 41:753–772.
Gao SZ, Schroeder JS, Alderman EL, et al.: Prevalence of accelerated coronary artery disease in heart transplant survivors. Comparison of cyclosporine and azathioprine regimens. Circulation 1989, 80(Suppl 3):100–105.
Olivari MT, Homans DC, Wilson RF, et al.: Coronary artery disease in cardiac transplant patients receiving triple drug immunosuppressive therapy. Circulation 1989, 80:111–115.
Uretsky BF, Murali S, Reddy PS, et al.: Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987, 76:827–834.
McGiffin DC, Savunen T, Kirklin JK, et al.: Cardiac transplant coronary artery disease. A multivariable analysis of pretransplantation risk factors for disease development and morbid events. J Thorac Cardiovasc Surg 1995, 109:1081–1088.
Yeung AC, Davis SF, Hauptmann PJ, et al.: Incidence and progression of transplant coronary artery disease over I year: results of a multicenter trial with use of intravascular ultrasound. J Heart Lung Transplant 1995, 14:S215-S220.
Rickenbacher PR, Pinto FJ, Chenzbraun A, et al.: Incidence and severity of transplant coronary artery disease early and up to 15 years after transplantation as detected by intravascular ultrasound. J Am Coll Cardiol 1995, 25:171–177.
Keogh AM, Valantine HA, Hunt SA, et al.: Impact of proximal or midvessel discrete coronary artery stenoses on survival after heart transplantation. J Heart Lung Transplant 1992, 11:892–901.
Uretsky BF, Kormos RL, Zerbe TR, et al.: Cardiac events after transplantation: incidence and predictive value of coronary arteriopathy. J Heart Lung Transplant 1992, 11:S45-S51.
Gao SZ, Hunt SA, Schroeder JS, et al.: Early development of accelerated graft coronary artery disease: risk factors and course. J Am Coll Cardiol 1996, 28:673–679.
Alexis JD, Pyo RT, Chereshnev I: Immunologic factors in transplant arteriopathy. Mt Sinai J Med 2003, 70:191–196.
Balantyne CM: Statins after cardiac transplantation: which statin, what dose and how low should we go? J Heart Lung Transplant 2000, 19:515–517.
Kapadia SR, Nissen SE, Ziada KM, et al.: Development of transplantation vasculopathy and progression of donor-transmitted atherosclerosis: comparison by serial intravascular ultrasound imaging. Circulation 1998, 98:2672–2678.
Jimenez J, Kapadia SR, Yamani MH, et al.: Cellular rejection and rate of progression of transplant vasculopathy: A 3-year serial intravascular ultrasound study. J Heart Lung Transplant 2001, 20:393–398.
Fang JC, Kinlay S, Beltrame J, et al.: Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 2002, 359:1108–1113.
Tanaka M, Mokhtari GK, Terry RD, et al.: Overexpression of human copper/zinc superoxide dismutase (SOD1) suppresses ischemia-reperfusion injury and subsequent development of graft coronary artery disease in murine cardiac grafts. Circulation 2004, 110(11 Suppl 1):II200-II206.
Murata S, Miniati DN, Kown MH, et al.: Superoxide dismutase mimetic m40401 reduces ischemia-reperfusion injury and graft coronary artery disease in rodent cardiac allografts. Transplantation 2004, 78:1166–1171.
Ferri C, Properzi G, Tomassoni G, et al.: Patterns of myocardial endothelin-1 expression and outcome after cardiac transplantation. Circulation 2002, 105:1768–1771.
Laberrere CA, Nelson DR, Park JW: Pathologic markers of allograft vasculopathy: insight into the pathophysiology of allograft chronic rejection. Curr Opin Cardiol 2001, 16:110–117.
Labarrere CA, Nelson DR, Cox CJ, et al.: Cardiac-specific troponin I levels and risk of coronary artery disease and graft failure following heart transplantation. JAMA 2000, 284:457–464.
Laberrere CA, Pitts D, Nelson DR, Faulk WP: Vascular tissue plasminogen activator and the development of coronary artery disease in heart transplant recipients. N Engl J Med 1995, 333:1111–1116.
Garvin MR, Labinaz M, Pels K, et al.: Arterial expression of the plasminogen activator system early after cardiac transplantation. Cardiovasc Res 1997, 35:241–249.
Wong CK, Ganz P, Miller L, et al.: Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: a multicenter prospective ultrasound study. J Heart Lung Transplant 2001, 20:385–392.
Lim TT, Liang DH, Botas J, et al.: Role of compensatory enlargement and shrinkage in transplant coronary artery disease: serial intravascular ultrasound study. Circulation 1997, 95:885–859.
Pethig K, Heublein B, Meliss RR, et al.: Volumetric remodeling of the proximal left coronary artery: early versus late after heart transplantation. J Am Coll Cardiol 1999, 34:197–203.
Tsutsui H, Ziada KM, Schoenhagen P, et al.: Lumen loss in transplant coronary artery disease is a biphasic process involving early intimal thickening and late constrictive remodeling: results from a 5 year serial intravascular ultrasound study. Circulation 2001, 104:653–657.
Vassalli G, Gallino A, Weis M, von Scheidt W, et al.: Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. Eur Heart J 2003, 24:1180–1188.
Caforio AL, Tona F, Fortina AB, et al.: Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: multivariate risk factor analysis and role of immunosuppression. Am J Transplantation 2004, 4:962–970.
Vamvakopoulos J, Hayry P: Cytomegalovirus and transplant arteriopathy: evidence for a link is mounting but the jury is still out. Transplantation 2003, 75:742–743.
Opelz G, Wujciak T: The influence of HLA compatibility on graft survival. Collaborative Transplant Study. N Engl J Med 1994, 330:816–819.
Gullestad L, Simonsen S, Ueland T, et al.: Possible role of proinflammatory cytokines in heart allograft coronary artery disease. Am J Cardiol 1999, 8:999–1003.
Labarrere CA, Nelson DR, Miller SJ, et al.: Value of serum-soluble intercellular adhesion molecule-1 for the noninvasive risk assessment of transplant coronary artery disease, posttransplant ischemic events, and cardiac graft failure. Circulation 2000, 102:1549–1555.
Ballantyne CM, Mainolfi EA, Young JB, et al.: Relationship of increased levels of circulating intercellular adhesion molecule 1 after heart transplantation to rejection: human leukocyte antigen mismatch and survival. J Heart Lung Transplant 1994, 13:597–603.
Vasilescu ER, Ho EK, de la Torre L, et al.: Anti-HLA antibodies in heart transplantation. Transplant Immunol 2004, 12:177–183.
Petrossian GA, Nichols AB, Marboe CC, et al.: Relationship between survival and development of coronary artery disease and anti-HLA antibodies after Cardiac Transplantation. Circulation 1989, 80:III122-III125.
Reed EF, Hong B, Ho E, et al.: Monitoring of soluble HLA allo-antigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation 1996, 61:566–572.
Michaels PJ, Espejo ML, Kobashigawa J, et al.: Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant 2003, 22:58–69.
Rose ML: Role of antibodies in transplant-associated cardiac allograft vasculopathy. Z Kardiol 2000, 89(Suppl 9):IX/11-IX15.
Jurcevic S, Ainsworth ME, Pomerance A, et al.: Antivimentin antibodies are an independent predictor of transplant-associated coronary artery disease after cardiac transplantation. Transplantation 2001, 71:886–892.
Collins AD, Ationu A: The role of anti-endothelial antibodies in the immunopathogenesis of transplant associated coronary artery disease. Int J Mol Med 1998, 1:439–452.
Faulk WP, Rose M, Meroni PL, et al.: Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts. Hum Immunol 1999, 60:826–832.
Grattan MT, Moreno-Cabral CE, Starnes VA, et al.: Cytomegalovirus infection is associated with cardiac allograft rejection and artherosclerosis. JAMA 1989, 261:3561.
Potena L, Grigioni F, Ortolani P, et al.: Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study. Transplantation 2003, 75:839–843.
Petrakopoulou P, Kubrich M, Pehlivanli S, et al.: Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function. Circulation 2004, 110(11 Suppl 1):II207-II212.
Weis M, Kledal TN, Lin KY, et al.: Cytomegalovirus infection impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine in transplant arteriosclerosis. Circulation 2004, 109:500–505.
Shirali GS, Ni J, Chinnock RE, et al.: Association of viral genome with graft loss in children after cardiac transplantation. N Engl J Med 2001, 244:1498–1503.
Yousufuddin M, Yamani MH: The renin-angiotensin hypothesis for the pathogenesis of cardiac allograft vasculopathy. Int J Cardiol 2004, 95:123–127.
Richter MH, Richter HR, Olbrich HG, et al.: Two good reasons for an angiotensin-II type 1 receptor blockade with losartan after cardiac transplantation: reduction of incidence and severity of transplant vasculopathy. Transplant Int 2003, 16:26–32.
Kobayashi J, Crawford S, Backer CL, et al.: Captopril reduces graft coronary artery disease in a rat heterotropic transplant model. Circulation 1993, 88:286–290.
Furukawa Y, Matsumori A, Hirozane T, et al.: Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserve graft status in murine model. A comparative study with captopril. Circulation 1996, 93:333–339.
Crawford SE, Mavroudis C, Backer CL, et al.: Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels. J Heart Lung Transplant 2004, 23:666–673.
Ventura HO, Mehra MR: C-Reactive protein and cardiac allograft vasculopathy. Is inflammation the critical link? J Am Coll Cardiol 2003, 42:483–485.
Hognestad A, Endresen K, Wergeland R, et al.: Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients. J Am Coll Cardiol 2003, 42:477–482.
Labarrere CA, Lee JB, Nelson DR, et al.: C-reactive protein, arterial endothelial activation, and development of transplant coronary artery disease: a prospective study. Lancet 2002, 360:1462–1467.
Calabro P, Willerson JT, Yeh ET: Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation 2003, 108:1930–1932.
Hollenberg SM, Klein LW, Parrillo JE, et al.: Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death. Circulation 2001, 104:3091–3096.
Andriambeloson E, Pally C, Hengerer B, et al.: Transplantation-induced endothelial dysfunction as studied in rat aorta allografts. Transplantation 2001, 72:1881–1889.
Hollenberg SM, Klein LW, Parrillo JE, et al.: Changes in coronary endothelial function predict progression of allograft vasculopathy after heart transplantation. J Heart Lung Transplant 2004, 23:265–271.
Davis SF, Yeung AC, Meredith IT, et al.: Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant. Circulation 1996, 93:457–462.
Labarrere CA, Nelson DR, Faulk WP: Endothelial activation and development of coronary artery disease in transplanted human hearts. JAMA 1997, 278:1169–1175.
Methe H, Zimmer E, Grimm R, et al.: Evidence for a role of toll-like receptor 4 in development of chronic allograft rejection after cardiac transplantation. Transplantation 2004, 78:1324–1331.
Shi C, Lee WS, He Q, Zhang D, et al.: Immunologic basis of transplant-associated arteriosclerosis. Proc Natl Acad Sci U S A 1996, 93:4051–4056.
Shi C, Feinberg MW, Zhang D, et al.: Donor MHC and adhesion molecules in transplant arteriosclerosis. J Clin Invest 1999, 103:469–474.
Dietrich H, Hu Y, Zou Y, et al.: Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1. Arterioscler Thromb Vasc Biol 2000, 20:343–352.
Raisanen-Sokolowski A, Glysing-Jensen T, Koglin J, et al.: Reduced transplant arterioscleross in murine cardiac allografts placed in interferon gamma knockout recipients. Am J Pathol 1998, 152:359–365.
Koglin J, Glysing-Jensen T, Gadiraju S, et al.: Attenuated cardiac allograft vasculopathy in mice with targeted depletion of transcription factor stat 4. Circulation 2000, 101:1034–1039.
Gao W, Topham PS, King JA, et al.: Targeting of the chemokine receptor CCR 1 suppresses the development of acute and chronic cardiac allograft rejection. J Clin Invest 2000, 105:35–44.
Gao W, Faia KL, Csizmadia V, et al.: Beneficial effects of targeting CCR5 in allograft recipients. Transplantation 2001, 72:1199–1205.
Raisanen-Sokolowski, Glysing-Jensen T, Russel ME: Leukocyte suppressing influences of interleukin 10 in cardiac allografts: insights from IL-10 knockout mice. Am J Pathol 1998, 153:1491–1500.
Tanaka M, Terry RD, Mokhtari GK, et al.: Suppression of graft coronary artery disease by a brief treatment with a selective epsilonPKC activator and a deltaPKC inhibitor in murine cardiac allografts. Circulation 2004, 110(11 Suppl 1):II194-II199.
Ventura HO, White CJ, Jain SP, et al.: Assessment of intracoronary morphology in cardiac transplant recipients by angioscopy and intravascular ultrasound. Am J Cardiol 1993, 72:805–809.
St Goar FG, Pinto FJ, Alderman EL, et al.: Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of “angiographically silent” intimal thickening. Circulation 1992, 85:979–987.
Rickenbacher PR, Pinto FJ, Lewis NP, et al.: Prognostic importance of intimal thickness as measured by intracoronary ultrasound after cardiac transplantation. Circulation 1995, 92:3445–3452.
Rickenbacher PR, Pinto FJ, Chenzbraun A, et al.: Incidence and severity of transplant coronary artery disease early and up to 15 years after transplantation as detected by intravascular ultrasound. J Am Coll Cardiol 1995, 25:171–177.
Mohiaddin RH, Bogren HG, Lazim F, et al.: Magnetic resonance coronary angiography in heart transplant recipients. Coron Artery Dis 1996, 7:591–597.
Muehling OM, Wilke NM, Panse P, et al.: Reduced myocardial perfusion reserve and transmural perfusion gradient in heart transplant arteriopathy assessed by magnetic resonance imaging. J Am Coll Cardiol 2003, 42:1054–1060.
Knollmann RD, Bocksch W, Spiegelsberger S, et al.: Electron bean computed tomography in the assessment of coronary artery disease after heart transplantation. Circulation 2000, 101:2078–2082.
Ludman PF, Lazem F, Barbir M, et al.: Incidence and clinical relevance of coronary calcification detection by electron beam computed tomography in heart transplant recipients. Eur Heart J 1999, 20:303–308.
Ratliff NB, Jorgensen CR, Gobel FL, et al.: Lack of usefulness of electron beam computed tomography for detecting coronary allograft vasculopathy. Am J Cardiol 2004, 93:202–206.
Bae KT, Hong C, Takahashi N, et al.: Multi-detector ro computed tomographic angiography in pediatric heart transplant recipients: Initial observations. Transplantation 2004, 77:599–602.
Spes CH, Mudra H, Schnaack SD, et al.: Dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy: a comparison with angiography and intravascular ultrasound. Am J Cardiol 1996, 78:168–174.
Spes CH, Klauss V, Mudra H, et al.: Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound. Circulation 1999, 100:509–515.
Bacal F, Moreira L, Souza G, et al.: Dobutamine stress echocardiography predicts cardiac events or death in asymptomatic patients long-term after heart transplantation: 4-year prospective evaluation. J Heart Lung Transplant 2004, 23:1238–1244.
Kobashigawa JA, Katznelson S, Laks H, et al.: Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995, 333:621–627.
Wenke K, Meiser B, Thiery J, et al.: Simvastatin reduces graft vessel disease and mortality after heart transplantation: a four-year randomized trial. Circulation 1997, 96:1398–1402.
Wenke K, Meiser B, Thiery J, et al.: Simvastatin initiated early after heart transplantation. 8 year prospective experience. Circulation 2003, 107:93–97.
Mehra MR, Uber PA, Vivekananthan K, et al.: Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection. J Am Coll Cardiol 2002, 40:1609–1614.
Keogh A, Macdonald P, Kaan A, et al.: Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation. J Heart Lung Transplant 2000, 19:529–537.
Wu AH, Ballantyne CM, Short BC, et al.: Statin use and risks of death or fatal rejection in the Heart Translant Lipid Registry. Am J Cardiol 2005, 95:367–372.
Valantine HA, Gao SZ, Menon SG, et al.: Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study. Circulation 1999, 100:61–66.
Valantine HA, Luikart H, Doyle R, et al.: Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone. Transplantation 2001, 72:1647–1652.
Randovancevic B, Vrtovec B: Sirolimus therapy in cardiac transplantation. Transplantation Proc 2003, 35 (Suppl 3A):171S-176S.
Mancini D, Pinney S, Burkhoff D, et al.: Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation 2003, 108:48–53.
Keogh A, Richardson M, Ruygrok P, et al.: Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation 2004, 110:2694–2700.
Eisen HJ, Tuzcu EM, Dorent R, et al.: Everolimus for the prevention of allograft rejection and vasculopathy in cardiac transplant recipients. N Engl J Med 2003, 349:847–858.
Halle AA 3rd, DiSciascio G, Massin EK, et al.: Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. J Am Coll Cardiol 1995, 26:120–128.
Benza RL, Zoghbi GJ, Tallaj J, et al.: Palliation of allograft vasculopathy with transluminal angioplasty: a decade of experience. J Am Coll Cardiol 2004, 43:1973–1981.
Fedak PW, Rao V, Verma S, et al.: Combined endothelial and myocardial protection by endothelin antagonism enhances transplant allograft preservation. J Thorac Cardiovasc Surg 2005, 129:407–415.
Wang CY, Aronson I, Takuma S, et al.: cAMP pulse during preservation inhibits the late development of cardiac isograft and allograft vasculopathy. Circ Res 2000, 86:982–988.
Iwata A, Sai S, Moore M, et al.: Gene therapy of transplant arteriopathy by liposome-mediated transfection of endothelial nitric oxide synthase. J Heart Lung Transplant 2000, 19:1017–1028.
School FG, Sen L, Drinkwater DC, et al.: Effects of human tissue plasminogen gene transfer on allograft coronary atherosclerosis. J Heart Lung Transplant 2001, 20:322–329.
Suzuki J, Isobe M, Yamazaki S, et al.: Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation. J Heart Lung Transplant 1997, 16:1141–1148.
Orosz CG, Ohye RG, Pelletier RP, et al.: Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces long-term murine cardiac allograft acceptance. Transplantation 1993, 56:453–460.
Russell PS, Chase CM, Winn HJ, et al.: Coronary atherosclerosis in transplanted mouse hearts. III. Effects of recipient treatment with a monoclonal antibody to interferon-gamma. Transplantation 1994, 57:1367–1371.
Wang CY, Mazer SP, Minamoto K, et al.: Suppression of murine cardiac allograft arteriopathy by long term blockade of CD40-CD154 interactions. Circulation 2002, 105:1609–1614.
Saiura A, Sata M, Hiasa K, et al.: Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy. Arterioscler Thromb Vasc Biol 2004, 24:1886–1890.
Yamoura K, Ito K, Tsukioka K, et al.: Suppression of acute and chronic rejection by hepatocyte growth factor in a murine model of cardiac transplantation: induction of tolerance and prevention of cardiac allograft vasculopathy. Circulation 2004, 110:1650–1657.
El-Sawy T, Belperio JA, Strieter RM, et al.: Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection. Circulation 2005, 112:320–331.
Nykanen AI, Krebs R, Tikkanen JM, et al.: Combined vascular endothelial growth factor and platelet-derived growth factor inhibition in rat cardiac allografts: beneficial effects on inflammation and smooth muscle cell proliferation. Transplantation 2005, 79:182–189.
Nykanen AI, Krebs R, Saaristo A, et al.: Angiopoietin-1 protects against the development of cardiac allograft arteriosclerosis. Circulation 2003, 107:1308–1314.
Isobe M, Suzuki JI, Morishita R, et al.: Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotide. Nat Med 1997, 3:900–903.
Kawauchi M, Suzuki J, Morishita R, et al.: Gene therapy for attenuating cardiac allograft arteriopathy using ex vivo E2F decoy transfection by HVJ-AVE-liposome method in mice and nonhuman primates. Circ Res 2000, 87:1063–1068.
Tsukioka K, Suzuki J, Fujimori M, et al.: Expression of matrix metalloproteinases in cardiac allograft vasculopathy and its attenuation by anti MMP-2 ribozyme gene transfection. Cardiovasc Res 2002, 56:472–478.
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Dhaliwal, A., Thohan, V. Cardiac allograft vasculopathy: The achilles’ heel of long-term survival after cardiac transplantation. Curr Atheroscler Rep 8, 119–130 (2006). https://doi.org/10.1007/s11883-006-0049-1
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DOI: https://doi.org/10.1007/s11883-006-0049-1