2-Methoxyestradiol reduces monocyte adhesion to aortic endothelial cells in ovariectomized rats.
2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with no affinity for estrogen receptors. It inhibits cell proliferation, thus is a potentially useful drug to block the progression of atherosclerosis. As a first step to examining the anti-atherosclerotic effects of 2-ME, we investigated monocyte adhesion to aortic endothelial cells, which is considered a prerequisite to atherosclerosis in vivo. Eight-week-old Sprague-Dawley rats were ovariectomized then treated by slow-release pellets with placebo, 17-beta-estradiol (5 microg/day), low-dose 2-ME (10 microg/day), or high-dose 2-ME (100 microg/day). After 6 weeks, en face analysis showed an increased number of monocytes adhering to endothelial cells of the thoracic aorta in ovariectomized rats compared with sham-operated controls. This increase was predominantly inhibited by treatment with 17beta-estradiol, and low-dose or high-dose 2-ME. The observed effects were unrelated to changes in serum lipids, blood glucose, or blood pressure. Our data suggested that 2-ME mediates the anti-atherosclerotic actions of estradiol at least in part by preventing monocyte adhesion to the aortic endothelium.
Kurokawa
Atsuko
A
Department of Gynecology, Juntendo University, School of Medicine, Tokyo, Japan.
Azuma
Kosuke
K
Mita
Tomoya
T
Toyofuku
Yukiko
Y
Fujitani
Yoshio
Y
Hirose
Takahisa
T
Iwabuchi
Kazuhisa
K
Ogawa
Hideoki
H
Takeda
Satoru
S
Kawamori
Ryuzo
R
Watada
Hirotaka
H
D000077584:2-Methoxyestradiol; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D019540:Area Under Curve; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010052:Ovariectomy; D017698:Postmenopause; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood