Estrogen increases apoptosis in the arterial wall in a murine atherosclerosis model.
OBJECTIVE
To investigate the effect of estrogen (E) on vascular apoptosis during atherosclerotic plaque formation.


METHODS
Laboratory study using a murine atherosclerosis model.


METHODS
Academic research center.


METHODS
Female mice homozygous for null alleles of LDL receptor (LDL-R(-/-)) in a C57BL/6 background. LDL-R(-/-) mice develop atherosclerosis in a predictable manner when fed a high cholesterol diet.


METHODS
Eight-week-old female LDL-R(-/-) mice (n = 68) were ovariectomized, and implanted subcutaneously with 90-day release pellets containing 0.5 mg of 17beta-estradiol (E(2)) or placebo. Four animals were evaluated at the initiation of the study. Thereafter, four animals from each group were sacrificed weekly for 8 weeks and their aortas studied.


METHODS
The effect of E(2) on atherosclerotic plaque development, apoptosis, and cell proliferation was examined in the aorta of ovariectomized LDL-R(-/-) mice that were fed a high cholesterol diet.


RESULTS
Mice treated with E(2) displayed a delay in atherosclerotic plaque formation, associated with an increase in DNA strand breaks in the arterial wall indicative of increased apoptosis, compared to placebo-treated mice. The two groups did not differ in mitotic activity.


CONCLUSIONS
In female LDL-R(-/-) mice fed a high cholesterol diet, ovariectomy is associated with increased atherogenesis. The effect of ovariectomy on atherogenesis is reversed by E(2) treatment. In addition to delayed atherogenesis, E(2) treatment of ovariectomized LDL-R(-/-) mice results in an increase in apoptosis in the aortic wall without an effect on the mitotic activity. Our findings suggest that vascular effects of E may be in part mediated by a proapoptotic activity.
Seli
Emre
E
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063 , USA.
Guzeloglu-Kayisli
Ozlem
O
Kayisli
Umit A
UA
Kizilay
Gulnur
G
Arici
Aydin
A
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D011973:Receptors, LDL / Q000172:deficiency
D004967:Estrogens; D011973:Receptors, LDL