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(Circulation. 2001;104:2615.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Transplant Coronary Artery Disease

A Novel Model Independent of Cellular Alloimmune Response

Bernard Cantin, MD PhD; Peizhong Wen, MD; Dening Zhu, MD; Michelle Dai, MSc; Shyam N. Panchal, BSc; Margaret E. Billingham, MD; Judith K. Gwathmey, VMD PhD; Hannah A. Valantine, MD

From the Division of Cardiovascular Medicine (B.C., P.W., D.Z., M.D., S.N.P., H.A.V.) and the Department of Pathology (M.E.B.), Stanford University School of Medicine, Stanford, Calif, and Gwathmey Inc, Cambridge, Mass (J.K.G.).

Correspondence to Dr Hannah A. Valantine, MD, MRCP, Division of Cardiovascular Medicine, Falk Building, Cardiovascular Research Center, 300 Pasteur Dr, Stanford, CA 94305-5406. E-mail hvalantine{at}stanford.edu

Background Allograft coronary atherosclerosis (TxCAD) is the leading cause of death after the first year after transplantation. TxCAD is believed to be a form of chronic rejection of the cardiac allografts. This study was undertaken to determine whether TxCAD could develop in the absence of a cellular alloimmune response.

Methods and Results Inbred lean Zucker rats (>26 generations) served as donors and recipients of the cardiac grafts. Donor hearts were explanted at 60 or 90 days. Explanted hearts were processed for coronary artery histological analysis. Cytokine expression was determined by reverse transcription–polymerase chain reaction, and the presence of T cells within the explanted hearts was evaluated by immunohistochemistry. Forty-six transplantations were made, and TxCAD developed in all but one of the transplanted hearts. Overall, one third of the vessels examined were affected by TxCAD, and in roughly half of these vessels, the disease was severe. Native hearts were free of atherosclerosis. Interleukin-2 was absent from the transplanted hearts, and T cells were present in minimal amounts (<1 per low-power field).

Conclusions TxCAD developed in the absence of a cellular alloimmune response in these genetically similar donors and recipients. The observed TxCAD was significant and comparable to what is found in rat allografting models.

Key Words: transplantation • immunology • interleukins • coronary disease • immunohistochemistry

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