© 1998 American Heart Association, Inc.
Original Contributions |
Upregulation of Estrogen Receptor-
Expression in Rabbit Cardiac Allograft
From the Departments of Surgery, Physiology and Biophysics (P.W.R.) and Lombardi Cancer Center (M.B.M., A.S.), Georgetown University Medical Center, Washington, DC.
Correspondence to Marie L. Foegh, MD, DSc, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Washington DC 20007. E-mail mfoegh{at}aol.com
Abstract—Estrogen receptor
(ER) expression has been detected in different tissues, and
estradiol-17ß treatment protects against experimental transplant
arteriosclerosis. In this study, ER- 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- protein was shown in the coronary arteries of the
cardiac allografts by immunohistochemistry with the use of a mouse
anti-human ER- 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- antisense riboprobe (pOR 300) proved
that the basal expression of ER- mRNA is similar in the nongrafted
aorta of both recipients and donors. A marked increase of ER- 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-. This is the first observation of ER- upregulation in the
allograft vasculature and may relate to the allograft
cardiovascular protective effects of estrogen.
Key Words: cardiac allograft • artery, coronary • estrogen receptor • gene expression
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