Upregulation of estrogen receptor-alpha expression in rabbit cardiac allograft.
Estrogen receptor (ER) expression has been detected in different tissues, and estradiol-17beta treatment protects against experimental transplant arteriosclerosis. In this study, ER-alpha 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-alpha protein was shown in the coronary arteries of the cardiac allografts by immunohistochemistry with the use of a mouse anti-human ER-alpha 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 32P-labeled ER-alpha antisense riboprobe (pOR 300) proved that the basal expression of ER-alpha mRNA is similar in the nongrafted aorta of both recipients and donors. A marked increase of ER-alpha 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-alpha. This is the first observation of ER-alpha upregulation in the allograft vasculature and may relate to the allograft cardiovascular protective effects of estrogen.
Lou
H
H
Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
Martin
M B
MB
Stoica
A
A
Ramwell
P W
PW
Foegh
M L
ML
D000818:Animals; D005786:Gene Expression Regulation; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics; D014184:Transplantation, Homologous; D015854:Up-Regulation
D012333:RNA, Messenger; D011960:Receptors, Estrogen