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Satoshi Saito
Noboru Motomura
Edward A. Lefrak
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J Thorac Cardiovasc Surg 1997;114:803-810
© 1997 Mosby, Inc.


CARDIAC AND PULMONARY REPLACEMENT

SPECIFIC EFFECTS OF ESTROGEN ON GROWTH FACTOR AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II ANTIGEN EXPRESSION IN RAT AORTIC ALLOGRAFT

Satoshi Saito , MD, Noboru Motomura , MD, PhD, Hong Lou , MD, Peter W. Ramwell , PhD, Marie L. Foegh , MD, DSc, Sponsor:, Edward A. Lefrak , MD, From the Department of Surgery and the Department of Physiology and Biophysics, Georgetown University Medical Center, Washington D.C.

Supported by the Ernst Schering Research Foundation and National Institutes of Health grant R01HL58896.

Received for publication May 7, 1997 revisions requested June 30, 1997; revisions received July 30, 1997 accepted for publication July 30, 1997. Address for reprints: Marie L. Foegh, MD, DSc, Georgetown University Medical Center, 4000 Reservoir Rd., N.W., Building D, Room 397, Washington, DC 20007.

Abstract

Objective: Transplant arteriosclerosis is the major determinant for long-term survival of cardiac transplants. Estradiol treatment inhibits transplant arteriosclerosis. The objective of this study is to determine, in the absence of immunosuppression, the temporal effect of estradiol treatment on the expression of insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen in rat aortic allografts. Methods: Orthotopic abdominal aortic allograft transplantation was performed in male rats with Brown-Norway rats used as donors and Lewis rats as recipients. The recipients (n = 50) were treated with estradiol 20 µg/kg per day or placebo by osmotic minipump for 2 days before the operation and until they were put to death on postoperative days 1, 3, 7, 14, or 21. The allografts were harvested and insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen expression were determined by immunohistochemical staining. Myointimal thickening was measured by morphometric analysis. Results: In the placebo-treated group, insulin-like growth factor protein progressively increased in all three layers of the allograft, whereas platelet-derived growth factor protein peaked at day 3 and basic fibroblast growth factor protein increased only moderately. Estradiol treatment inhibited the continuous increase in insulin-like growth factor expression, the peak in platelet-derived growth factor expression at day 3, the moderate basic fibroblast growth factor increase at day 21, and major histocompatibility complex class II antigen expression in all three layers of the allograft at day 21. Intimal thickening of allografts from estradiol-treated recipients was twofold to threefold less than that of the placebo-treated recipients at day 21. Conclusion: The development of transplant arteriosclerosis is associated with an early alloimmune response involving sustained increase in insulin-like growth factor expression. Estradiol treatment of the recipient inhibits transplant arteriosclerosis and suppresses insulin-like growth factor and major histocompatibility complex class II antigen expression but not platelet-derived growth factor or basic fibroblast growth factor in all three layers of the allograft during the early posttransplantation alloimmune rejection phase.




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