Upregulation of Estrogen Receptor-α Expression in Rabbit Cardiac Allograft

Abstract

Abstract —Estrogen receptor (ER) expression has been detected in different tissues, and estradiol-17β treatment protects against experimental transplant arteriosclerosis. In this study, ER-α expression in the rabbit hearts and attached aortas before and after cardiac-aorta allograft transplantation was examined. Ten male New Zealand White rabbits were transplanted with cardiac-aorta allografts from male Dutch Belted rabbits. This transplant arteriosclerosis model uses a 0.5% cholesterol diet and immunosuppression with cyclosporin A (10 mg · kg −1 · d −1 ) until euthanatization 42 days later. The cardiac grafts with the attached aorta were harvested. Strong staining of ER-α protein was shown in the coronary arteries of the cardiac allografts by immunohistochemistry with the use of a mouse anti-human ER-α monoclonal antibody (ID5). In contrast, both the nongrafted hearts of the recipients and donor hearts expressed only weak staining. RNase protection assay with the use of a 32 P–labeled ER-α antisense riboprobe (pOR 300) proved that the basal expression of ER-α mRNA is similar in the nongrafted aorta of both recipients and donors. A marked increase of ER-α mRNA was observed in the allograft aorta compared with the nongrafted aorta (289±69%, P <0.02) by reverse transcription and polymerase chain reaction. The DNA sequence analysis confirmed that the polymerase chain reaction–amplified fragment corresponded to ER-α. This is the first observation of ER-α upregulation in the allograft vasculature and may relate to the allograft cardiovascular protective effects of estrogen.