Abstract
Rat aortic allografts immunosuppressed with cyclosporin — but not with azathioprine or steroids — develop an early inflammatory lesion in the subendothelial space. This “endothelialitis” is followed by an influx of proliferating smooth muscle cells into the intima, resulting in intimal thickening and accelerated arteriosclerosis. Administration of azathioprine and steroids largely ameliorates the development of the accelerated lesion. Similar endothelialitis and accelerated arteriosclerosis have been observed previously in the autopsy material of cardiac transplant recipients. Our results confirm the suggestion that the development of accelerated allograft arteriosclerosis is most likely linked to cyclosporin administration.
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Aherne WA, Dunnill MS (1982) Morphometry. Arnold, London
Alonso DR, Storek PK, Minick R (1977) Studies on the pathogenesis of atheroarteriosclerosis induced in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia. Am J Pathol 87: 415–435
Billingham RE (1989) Graft coronary disease: the lesions and the patients. Transplant Proc 21: 3665–3666
Bunchman TE, Brookshire CA (1991) Smooth muscle cell proliferation by conditioned media from cyclosporine-treated endothelial cells: a role of endothelin. Transplant Proc 23: 967–968
Cramer DV, Qian S, Harnaha J, Chapman FA, Starzl TE, Makowka L (1989) Accelerated graft arteriosclerosis is enhanced by sensitization of the recipient to donor lymphocytes. Transplant Proc 21: 3714–3715
Demetris AJ, Lasky S, Theil DH van, Starzl TE, Dekker A (1985) Pathology of hepatic trasnplantation. A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid combination. Am J Pathol 118: 151–158
Demetris AJ, Zerbe T, Banner B (1989) Morphology of solid organ allograft arteriopathy: identification of proliferating intimal cell populations. Transplant Proc 21: 3667–3669
Ferry B, Halttunen J, Leszczynski D, Schellekens H, Meide P v.d., Häyry P (1987) Impact of class II major histocompatibility complex antigen expression on the immunogenic potential of isolated rat vascular endothelial cells. Transplantation 44: 499–503
Foegh ML (1990) Chronic rejection-graft arteriosclerosis. Transplant Proc 22: 119–122
Herskowitz A, Tamura F, Ueda K, Neumann DA, Slepian M, Rose NR, Beschorner WE, Baumgartner WA, Reitz BR, Sell KW, Ahmed-Ansari A (1989) Induction of donor major histocompatibility complex antigens in coronary arterial vessels: mechanism of arterial vasculitis in rat allografts treated with cyclosporine. J Heart Transplant 8: 11–19
Lim SM, Kogure K, White DJ (1990) Steroid treatment depresses the production of transplantation tolerance. Transplant Proc 22: 1989–1990
Mennander A, Tiisala S, Halttunen J, Yilmaz S, Paavonen T, Häyry P (1991) Chronic rejection in rat aortic allografts. An experimental model for transplant arteriosclerosis. Arteriosclerosis Thrombosis 11: 671–680
Palmer DC, Tsai CC, Roodman ST, Codd JE, Miller LW, Sarafian JE, Williams GA (1985) Heart graft arteriosclerosis: an ominous finding on endomyocardial biopsy. Transplantation 39: 385–388
Smith SH, Kirklin JK, Geer JC, Caulfield JB, McGiffin DC (1987) Arteritis in cardiac rejection after transplantation. Am J Cardiol 59: 1171–1173
Sommer BG, Innes JT, Whitehurst RM, Sharma HM, Ferguson RM (1985) Cyclosporine-associated renal arteriopathy resulting in loss of allograft function. Am J Surgery 149: 759–764
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Mennander, A., Tiisala, S., Paavonen, T. et al. Chronic rejection of rat aortic allograft. Transplant Int 4, 173–179 (1991). https://doi.org/10.1007/BF00335340
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DOI: https://doi.org/10.1007/BF00335340