The Regulation and Consequences of Immune-Mediated Cell Death in Atheromatous Diseases

Cardiovascular Toxicology

Volumn 3, Issue 3, 2003, Pages 269-282

  Choy, Jonathan C ^a   Podor, Thomas J ^a   Yanagawa, Bobby ^a   Lai, John C K ^a   Granville, David J ^a   Walker, David C ^a   McManus, Bruce M ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b ST PAUL S HOSPITAL   (Canada)

Author keywords

Apoptosis; Coronary artery disease; FasL; Granzyme B; T cell; Transplant vascular disease

Indexed keywords

FAS LIGAND; GRANZYME A; GRANZYME B; PERFORIN;

APOPTOSIS; ATHEROMATOSIS; CORONARY ARTERY DISEASE; EFFECTOR CELL; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOREGULATION; PATHOGENESIS; PRIORITY JOURNAL; RESTENOSIS; REVIEW; VASCULAR DISEASE;

ANIMALS; ARTERIOSCLEROSIS; CELL DEATH; CORONARY VESSELS; HUMANS; VASCULAR DISEASES;

EID: 0142085768     PISSN: 15307905     EISSN: None     Source Type: Journal    
DOI: 10.1385/CT:3:3:269     Document Type: Review

References (95)

1. Ross, R. (1999). Atherosclerosis: An inflammatory disease. N. Engl. J. Med. 340:115-126.
2. Wilson, J.E., Wood, S., McDonald, P., Kenyon, J., Dong, C., and McManus, B.M. (1997). Contribution of lipids to the pathogenesis of transplant vascular sclerosis. Transpl. Immunol. 5:247-250.
3. McDonald, P.C., Kenyon, J.A., and McManus, B.M. (1998). The role of lipids in transplant vascular disease. Lab. Invest. 78:1187-1201.
4. Choy, J.C., Granville, D.J., Hunt, D.W., and McManus, B.M. (2001). Endothelial cell apoptosis: Biochemical characteristics and potential implications for atherosclerosis. J. Mol. Cell. Cardiol. 33:1673-1690.
5. Kerr, J.F.R., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-245.
6. Granville, D.J., Carthy, C.M., Hunt, D.W., and McManus, B.M. (1998). Apoptosis: Molecular aspects of cell death and disease. Lab. Invest. 78:893-913.
7. Caplan, B.A., and Schwartz, C.J. (1973). Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta. Atherosclerosis 17:401-417.
8. Caplan, B.A., Gerrity, R.G., and Schwartz, C.J. (1974). Endothelial cell morphology in focal areas of in vivo Evans blue uptake in the young pig aorta. I. Quantitative light microscopic findings. Exp. Mol. Pathol. 21:102-117.
9. Somer, J.B., and Schwartz, C.J. (1971). Focal 3 H-cholesterol uptake in the pig aorta. Atherosclerosis 13:293-304.
10. Somer, J.B., and Schwartz, C.J. (1972). Focal (3 H)cholesterol uptake in the pig aorta. 2. Distribution of (3 H)cholesterol across the aortic wall in areas of high and low uptake in vivo. Atherosclerosis 16:377-388.
11. Weinbaum, S., Tzeghai, G., Ganatos, P., Pfeffer, R., and Chien, S. (1985). Effect of cell turnover and leaky junctions on arterial macromolecular transport. Am. J. Physiol. 248: H945-H960.
12. Tricot, O., Mallat, Z., Heymes, C., Belmin, J., Leseche, G., and Tedgui, A. (2000). Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 101:2450-2453.
13. Bombeli, T., Karsan, A., Tait, J.F., and Harlan, J.M. (1997). Apoptotic vascular endothelial cells become procoagulant. Blood 89:2429-2442.
14. Geng, Y.J. and Libby, P. (1995). Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme. Am. J. Pathol. 147:251-266.
15. Isner, J.M., Kearney, M., Bortman, S., and Passeri, J. (1995). Apoptosis in human atherosclerosis and restenosis. Circulation 91:2703-2711.
16. Bennett, M.R., Evan, G.I., and Schwartz, S.M. (1995). Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J. Clin. Invest. 95:2266-2274.
17. Pollman, M.J., Hall, J.L., Mann, M.J., Zhang, L., and Gibbons, G.H. (1998). Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat. Med. 4:222-227.
18. Blanc-Brude, O.P., Yu, J., Simosa, H., Conte, M.S., Sessa, W.C., and Altieri, D.C. (2002). Inhibitor of apoptosis protein survivin regulates vascular injury. Nat. Med. 8:987-994.
19. Kraemer, R. (2002). Reduced apoptosis and increased lesion development in the flow-restricted carotid artery of p75(NTR)-null mutant mice. Circ. Res. 91:494-500.
20. von der Thusen, J.H., van Vlijmen, B.J., Hoeben, R.C., Kockx, M.M., Havekes, L.M., van Berkel, T.J., and Biessen, E.A. (2002). Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53. Circulation 105:2064-2070.
21. Dong, C., Redenbach, D., Wood, S., Battistini, B., Wilson, J.E., and McManus, B.M. (1996). The pathogenesis of cardiac allograft vasculopathy. Curr. Opin. Cardiol. 11:183-190.
22. Lai, J.L., Tranfield, E.M., Walker, D.C., Dyck, J., Kerjner, A., Loo, S., et al. Ultrastructural evidence of early endothelial damage in coronary arteries of rat cardiac allografts. J. Heart Lung Transplant. in press.
23. Qian, Z., Hu, W., Liu, J., Sanfilippo, F., Hruban, R.H., and Baldwin, W.M., 3rd. (2001). Accelerated graft arteriosclerosis in cardiac transplants: complement activation promotes progression of lesions from medium to large arteries. Transplantation 72:900-906.
24. Fox, W.M., Hameed, A., Hutchins, G.M., Reitz, B.A., Baumgartner, W.A., Beschorner, W.E., and Hruban, R.H. (1993). Perforin expression localizing cytotoxic lymphocytes in the intimas of coronary arteries with transplant-related accelerated arteriosclerosis. Hum. Pathol. 24:477-482.
25. Yamani, M.H., Haji, S.A., Starling, R.C., Tuzcu, E.M., Ratliff, N.B., Cook, D.J., et al. (2002). Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased cellular rejection and poor long-term outcome. J. Am. Coll. Cardiol. 39:970-977.
26. Meckel, C.R., Anderson, T.J., Mudge, G.H., Mitchell, R.N., Yeung, A.C., Selwyn, A.P., et al. (1997). Hemostatic/fibrinolytic predictors of allograft coronary artery disease after cardiac transplantation. Vasc. Med. 2:306-312.
27. Sartori, T.M., Maurizio, P.G., Sara, P., Ugolino, L., Annalisa, A., Panagiotis, T., Massimo, F., and Antonio, G. (1999). Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation. J. Heart Lung Transplant. 18:693-700.
28. Miller, L.W., Dai, E., Nash, P., Liu, L., Icton, C., Klironomos, D., Fan, L., Nation, P.N., Zhong, R., McFadden, G., and Lucas, A. (2000). Inhibition of transplant vasculopathy in a rat aortic allograft model after infusion of antiinflammatory viral serpin. Circulation 101:1598-1605.
29. Garvin, M.R., Labinaz, M., Pels, K., Walley, V.M., Mizgala, H.F., and O'Brien, E.R. (1997). Arterial expression of the plasminogen activator system early after cardiac transplantation. Cardiovasc. Res. 35:241-249.
30. Warshofsky, M.K., Wasserman, H.S., Wang, W., Teng, P., Sciacca, R., Apfelbaum, M., et al. (1997). Plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1 are correlated with the presence of transplant coronary artery disease in cardiac transplant recipients. Am. J. Cardiol. 80:145-149.
31. Warshofsky, M.K., Dominguez, M., Eisenberg, M.S., Wasserman, H.S., Sciacca, R., Wang, W., et al. (2001). Elevated plasma tissue plasminogen activator and anti-THP-1 antibodies are independently associated with decreased graft survival in cardiac transplant recipients. Am. J. Cardiol. 88:30-34.
32. Scholl, F.G., Sen, L., Drinkwater, D.C., Laks, H., Ma, X.Y., Hong, Y.S., et al. (2001). Effects of human tissue plasminogen gene transfer on allograft coronary atherosclerosis. J. Heart Lung Transplant. 20:322-329.
33. McManus, B.M., Horley, K.J., Wilson, J.E., Malcom, G.T., Kendall, T.J., Miles, R.R., et al. (1995). Prominence of coronary arterial wall lipids in human heart allografts. Implications for pathogenesis of allograft arteriopathy. Am. J. Pathol. 147:293-308.
34. Susskind, B., Shomick, M.D., Iannotti, MR., Duffy, B., Mehrotra, P.T., Siegel, J.P., et al. (1996). Cytolytic effector mechanisms of human CD4+ cytotoxic T lymphocytes. Hum. Immunol. 45:64-75.
35. Seshiah, P.N., Kereiakes, D.J., Vasudevan, S.S., Lopes, N., Su, B.Y., Flavahan, N.A., et al. (2002). Activated monocytes induce smooth muscle cell death: role of macrophage colony-stimulating factor and cell contact. Circulation 105:174-180.
36. Boyle, J.J., Bowyer, D.E., Weissberg, P.L., and Bennett, M.R. (2001). Human blood-derived macrophages induce apoptosis in human plaque-derived vascular smooth muscle cells by Fas-ligand/Fas interactions. Arterioscl. Thromb. Vasc. Biol. 21:1402-1407.
37. Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., et al. (1997). Inhibition of death receptor signals by cellular FLIP. Nature 388:190-195.
38. Sata, M., Suhara, T., and Walsh, K. (2000). Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler. Thromb. Vasc. Biol. 20:309-316.
39. Sata, M. and Walsh, K. (1998). Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP. J Biol. Chem. 273:33103-33106.
40. Sata, M., Suhara, T., and Walsh, K. (2000). Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: Implications for vascular disease and therapy. Arterioscl. Thromb. Vasc. Biol. 20:309-316.
41. Chan, S.W., Hegyi, L., Scott, S., Cary, N.R., Weissberg, P.L., and Bennett, M.R. (2000). Sensitivity to Fas-mediated apoptosis is determined below receptor level in human vascular smooth muscle cells [see comments]. Circ. Res. 86:1038-1046.
42. Imanishi, T., McBride, J., Ho, Q., O'Brien, K.D., Schwartz, S.M., and Han, D.K. (2000). Expression of cellular FLICE-inhibitory protein in human coronary arteries and in a rat vascular injury model. Am. J. Pathol. 156:125-137.
43. Costain, D.J., Guha, A.K., Liwski, R.S., and Lee, T.D. (2001). Murine hypodense eosinophils induce tumour cell apoptosis by a granzyme B-dependent mechanism. Cancer Immunol. Immunother. 50:293-299.
44. Pham, C.T., MacIvor, D.M., Hug, B.A., Heusel, J.W., and Ley, T.J. (1996). Long-range disruption of gene expression by a selectable marker cassette. Proc. Natl. Acad. Sci. USA 93:13090-13095.
45. Young, J.D., Hengartner, H., Podack, E.R., and Cohn, Z.A. (1986). Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 44:849-859.
46. Motyka, B., Korbutt, G., Pinkoski, M.J., Heibein, J.A., Caputo, A., Hobman, M., et al. (2000). Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell 103:491-500.
47. Bleackley, R.C. and Heibein, J.A. (2001). Enzymatic control of apoptosis. Nat. Prod. Rep. 18:431-440.
48. Sun, J., Bird, C.H., Sutton, V., McDonald, L., Coughlin, P.B., De Jong, T.A., et al. (1996). A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic lymphocytes. J. Biol. Chem. 271:27802-27809.
49. Buzza, M.S., Hirst, C.E., Bird, C.H., Hosking, P., McKendrick, J., and Bird, P.I. (2001). The granzyme B inhibitor, PI-9, is present in endothelial and mesothelial cells, suggesting that it protects bystander cells during immune responses. Cell. Immunol. 210:21-29.
50. Young, J.L., Sukhova, G.K., Foster, D., Kisiel, W., Libby, P., and Schonbeck, U. (2000). The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1beta-converting enzyme (caspase-1) activity in human vascular smooth muscle cells. J. Exp. Med. 191:1535-1544.
51. a. Shi, C., Lee, W.S., He, Q., Zhang, D., Fletcher, D.L. Jr., Newell, J.B., and Haber, E. (1996). Immunologic basis of transplant-associated arteriosclerosis. Proc. Natl. Acad. Sci. USA 93:4051-4056.
52. b. Szeto, W.Y., Krasinskas, A.M., Kreisel, D., Krupnick, A.S., Popma, S.H., and Rosengard, B.R. (2002). Depletion of recipient CD4+ but not CD8+ T lymphocytes prevents the development of cardiac allograft vasculopathy. Transplantation 73:1116-1122.
53. c. Fischbein, M.P., Yun, J., Laks, H., Irie, Y., Fishbein, M.C., Espejo, M., Bonavida, B., and Ardehali, A. (2001). CD8+ lymphocytes augment chronic rejection in a MHC class II mismatched model. Transplantation 71:1146-1153.
54. Boyle, J.J. (1997). Association of coronary plaque rupture and atherosclerotic inflammation. J. Pathol. 181:93-99.
55. Jacob, T., Ascher, E., Hingorani, A., Khandros, Y., Tsemekhin, B., Zeien, L., et al. (2001). Differential proteolytic activity and induction of apoptosis in fibrous versus atheromatous plaques in carotid atherosclerotic disease. J. Vasc. Surg. 33:614-620.
56. Dong, C., Wilson, J.E., Winters, G.L., and McManus, B.M. (1996). Human transplant coronary artery disease: Pathological evidence for Fas- mediated apoptotic cytotoxicity in allograft arteriopathy. Lab. Invest. 74:921-931.
57. Subbotin, V., Sun, H., Aitouche, A., Salam, A., Valdivia, L.A., Fung, J.J., et al. (1999). Marked mitigation of transplant vascular sclerosis in FasLg1d (CD95L) mutant recipients. The role of alloantibodies in the development of chronic rejection. Transplantation 67:1295-1300.
58. Wang, T., Dong, C., Stevenson, S.C., Herderick, E.E., Marshall-Neff, J., Vasudevan, S.S., et al. (2002). Over-expression of soluble fas attenuates transplant arteriosclerosis in rat aortic allografts. Circulation 106:1536-1542.
59. Schiller, N.K., Boisvert, W.A., and Curtiss, L.K. (2002). Inflammation in atherosclerosis: Lesion formation in LDL receptor-deficient mice with perforin and Lyst(beige) mutations. Arterioscler. Thromb. Vasc. Biol. 22:1341-1346.
60. Nakajima, T., Schulte, S., Warrington, K.J., Kopecky, S.L., Frye, R.L., Goronzy, J.J., et al. (2002). T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation 105:570-575.
61. Hruban, R.H., Beschorner, W.E., Baumgartner, W.A., Augustine, S.M., Ren, H., Reitz, B.A., et al. (1990). Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Am. J. Pathol. 137:871-882.
62. Krupnick, A.S., Kreisel, D., Popma, S.H., Balsara, K.R., Szeto, W.Y., Krasinskas, A.M., et al. (2002). Mechanism of T cell-mediated endothelial apoptosis. Transplantation 74:871-876.
63. Choy, J.C., McDonald, P.C., Suarez, P.C., Hung, V.H., Wilson, J.E., McManus, B.M., et al. Granzyme B in atherosclerosis and transplant vascular disease: Association with cell death and atherosclerotic disease severity. Mod. Pathol. in press.
64. Gahring, L., Carlson, N.G., Meyer, E.L., and Rogers, S.W. (2001). Granzyme B proteolysis of a neuronal glutamate receptor generates an autoantigen and is modulated by glycosylation. J. Immunol. 166:1433-1438.
65. a. Casciola-Rosen, L., Andrade, F., Ulanet, D., Wong, W.B., and Rosen, A. (1999). Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity. J. Exp. Med. 190:815-826.
66. Hirsch, G.M., Kearsey, J., Burt, T., Karnovsky, M.J., and Lee, T. (1998). Medial smooth muscle cell loss in arterial allografts occurs by cytolytic cell induced apoptosis. Eur. J. Cardiothorac. Surg. 14:89-96; discussion 96-97.
67. Isik, F.F., McDonald, T.O., Ferguson, M., Yamanaka, E., and Gordon, D. (1992). Transplant arteriosclerosis in a rat aortic model. Am. J. Pathol. 141:1139-1149.
68. Hare, G.M., Lee, T.D., Jordan, J.L., and Hirsch, G.M. (1999). Medial cell apoptosis precedes the development of intimal hyperplasia after transient allogeneic exposure in a rat aortic allograft model of chronic rejection. Transplant. Proc. 31:1384-1385.
69. O'Neill, J.L., Lee, T.D., and Hirsch, G.M. (1999). CD8+ cytotoxic T lymphocytes are involved in inducing medial cell dropout via apoptosis in mouse aortic allografts. Transplant. Proc. 31:865-866.
70. O'Neill, J., Jordan, J.L., Zhou, J., Lee, T.D., and Hirsch, G.M. (2001). Impairment of cytolytic activity in allograft environment affects early medial cell loss but does not alter outcome of allograft arteriosclerosis. J. Heart Lung Transplant. 20:159.
71. Salonen, J.T., Yla-Herttuala, S., Yamamoto, R., Butler, S., Korpela, H., Salonen, R., et al. (1992). Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339:883-887.
72. Yla-Herttuala, S., Palinski, W., Butler, S.W., Picard, S., Steinberg, D., and Witztum, J.L. (1994). Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscl. Thromb. 14:32-40.
73. Caligiuri, G., Paulsson, G., Nicoletti, A., Maseri, A., and Hansson, G.K. (2000). Evidence for antigen-driven T-cell response in unstable angina. Circulation 102:1114-1119.
74. Fang, J.C., Kinlay, S., Behrendt, D., Hikita, H., Witztum, J.L., Selwyn, A.P., et al. (2002). Circulating autoantibodies to oxidized LDL correlate with impaired coronary endothelial function after cardiac transplantation. Arterioscl. Thromb. Vasc. Biol. 22:2044-2048.
75. Epperson, D.E. and Pober, J.S. (1994). Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells. J. Immunol. 153:5402-5412.
76. Biedermann, B.C. and Pober, J.S. (1998). Human endothelial cells induce and regulate cytolytic T cell differentiation. J. Immunol. 161:4679-4687.
77. Biedermann, B.C. and Pober, J.S. (1999). Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL. J. Immunol. 162:7022-7030.
78. Murray, A.G., Libby, P., and Pober, J.S. (1995). Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro. J. Immunol. 154:151-161.
79. Saikku, P., Leinonen, M., Mattila, K., Ekman, M.R., Nieminen, M.S., Makela, P.H., et al. (1998). Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 2:983-986.
80. Grayston, J.T. (1993). Chlamydia in atherosclerosis. Circulation 87:1408-1409.
81. Kalayoglu, M.V., Libby, P., and Byrne, G.I. (2002). Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. JAMA 288:2724-2731.
82. Benjamin, I.J., and McMillan, D.R. (1998). Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ. Res. 83:117-132.
83. Kleindienst, R., Xu, Q., Willeit, J., Waldenberger, F.R., Weimann, S., and Wick, G. (1993). Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. Am. J. Pathol. 142:1927-1937.
84. Kol, A., Sukhova, G.K., Lichtman, A.H., and Libby, P. (1998). Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. Circulation 98:300-307.
85. Kol, A., Bourcier, T., Lichtman, A.H., and Libby, P. (1999). Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J. Clin. Invest. 103:571-577.
86. Young, R.A. and Elliott, T.J. (1989). Stress proteins, infection, and immune surveillance. Cell 59:5-8.
87. Burian, K., Kis, Z., Virok, D., Endresz, V., Prohaszka, Z., Duba, J., et al. (2001). Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis. Circulation 103:1503-1508.
88. Zhu, J., Quyyumi, A.A., Rott, D., Csako, G., Wu, H., Halcox, J., et al. Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis. Circulation 103:1071-1075.
89. Mahdi, O.S., Horne, B.D., Mullen, K., Muhlestein, J.B., and Byrne, G.I. (2002). Serum immunoglobulin G antibodies to chlamydial heat shock protein 60 but not to human and bacterial homologs are associated with coronary artery disease. Circulation 106:1659-1663.
90. Pockley, A.G. (2002). Heat shock proteins, inflammation, and cardiovascular disease. Circulation 105:1012-1017.
91. Glaser, R., Lu, M.M., Narula, N., and Epstein, J.A. (2002). Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts. Circulation 106:17-19.
92. Tomita, S., Li, R.K., Weisel, R.D., Mickle, D.A., Kim, E.J., Sakai, T., et al. (1999). Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:II247-II256.
93. Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., et al. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. Natl. Acad. Sci. USA 98:10344-10349.
94. Muller, P., Pfeiffer, P., Koglin, J., Schafers, H.J., Seeland, U., Janzen, I., et al. (2002). Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation 106:31-35.
95. Assmus, B., Schachinger, V., Teupe, C., Britten, M., Lehmann, R., Dobert, N., et al. (2002). Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106:3009-3017.