This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Isik, F. F. Articles by Gordon, D. Search for Related Content PubMed PubMed Citation Articles by Isik, F. F. Articles by Gordon, D.

American Journal of Pathology, Vol 141, 1139-1149, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Transplant arteriosclerosis in a rat aortic model

FF Isik, TO McDonald, M Ferguson, E Yamanaka and D Gordon
Department of Pathology, University of Washington, Seattle.

Transplant arteriosclerosis (TA) has emerged as an obstacle to the long- term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte- /macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested.

This article has been cited by other articles:

				M. Rahmani, R. P. Cruz, D. J. Granville, and B. M. McManus Allograft Vasculopathy Versus Atherosclerosis Circ. Res., October 13, 2006; 99(8): 801 - 815. [Abstract] [Full Text] [PDF]

				O. Thaunat, A.-C. Field, J. Dai, L. Louedec, N. Patey, M.-F. Bloch, C. Mandet, M.-F. Belair, P. Bruneval, O. Meilhac, et al. Lymphoid neogenesis in chronic rejection: Evidence for a local humoral alloimmune response PNAS, October 11, 2005; 102(41): 14723 - 14728. [Abstract] [Full Text] [PDF]

				H. Sakihama, T. Masunaga, K. Yamashita, T. Hashimoto, M. Inobe, S. Todo, and T. Uede Stromal Cell-Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis Circulation, November 2, 2004; 110(18): 2924 - 2930. [Abstract] [Full Text] [PDF]

				T. Wang, C. Dong, S. C. Stevenson, E. E. Herderick, J. Marshall-Neff, S. S. Vasudevan, N. I. Moldovan, R. E. Michler, N. R. Movva, and P. J. Goldschmidt-Clermont Overexpression of Soluble Fas Attenuates Transplant Arteriosclerosis in Rat Aortic Allografts Circulation, September 17, 2002; 106(12): 1536 - 1542. [Abstract] [Full Text] [PDF]

				M. Sata, Z. Luo, and K. Walsh Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia J. Immunol., June 1, 2001; 166(11): 6964 - 6971. [Abstract] [Full Text] [PDF]

				E. Andriambeloson, M. Bigaud, E. O. Schraa, T. Kobel, V. Lobstein, C. Pally, and Hans-Gunter Zerwes Endothelial Dysfunction and Denudation in Rat Aortic Allografts Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 67 - 73. [Abstract] [Full Text] [PDF]

				J.-F. Legare, T. Issekutz, T. D. G. Lee, and G. Hirsch CD8+ T Lymphocytes Mediate Destruction of the Vascular Media in a Model of Chronic Rejection Am. J. Pathol., September 1, 2000; 157(3): 859 - 865. [Abstract] [Full Text] [PDF]

				M. V. Autieri, C. Carbone, and A. Mu Expression of Allograft Inflammatory Factor-1 Is a Marker of Activated Human Vascular Smooth Muscle Cells and Arterial Injury Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1737 - 1744. [Abstract] [Full Text] [PDF]

				M. Sata, T. Suhara, and K. Walsh 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., February 1, 2000; 20(2): 309 - 316. [Abstract] [Full Text] [PDF]

				G. M. Hirsch, J. Kearsey, T. Burt, M. J. Karnovsky, and T. Lee Medial smooth muscle cell loss in arterial allografts occurs by cytolytic cell induced apoptosis Eur. J. Cardiothorac. Surg., July 1, 1999; 14(1): 89 - 97. [Abstract] [Full Text] [PDF]

				F. C. Tanner, Z.-Y. Yang, E. Duckers, D. Gordon, G. J. Nabel, and E. G. Nabel Expression of Cyclin-Dependent Kinase Inhibitors in Vascular Disease Circ. Res., February 23, 1998; 82(3): 396 - 403. [Abstract] [Full Text] [PDF]

				J. Waltenberger, M. L. Akyurek, M. Aurivillius, A. Wanders, E. Larsson, B. Fellstrom, and K. Funa Ischemia-Induced Transplant Arteriosclerosis in the Rat: Induction of Peptide Growth Factor Expression Arterioscler. Thromb. Vasc. Biol., December 1, 1996; 16(12): 1516 - 1523. [Abstract] [Full Text]

				T Ohno, D Gordon, H San, V. Pompili, M. Imperiale, G. Nabel, and E. Nabel Gene therapy for vascular smooth muscle cell proliferation after arterial injury Science, August 5, 1994; 265(5173): 781 - 784. [Abstract] [PDF]