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Updated: Jul 14, 2026
Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized mice
Rami Abu-Fanne1, Amnon Brzezinski, Mordechai Golomb
1Cardiovascular Research Center, Hadassah Hebrew University Medical Center, Kiryat Hadassah, Jerusalem, Israel.
Objective:
The effects of estrogen and selective estrogen receptor modulators (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed the manner and mechanism by which estrogen and raloxifene affect homeostatic pathways in ovariectomized mice after acute arterial injury.
Design:
Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured.
Results:
Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively.
Conclusions:
Ovariectomy amplifies thrombosis. We found that 4 months of treatment with both estradiol and raloxifene attenuates intravascular thrombosis. The antithrombotic effect was accompanied by increased expression of cyclooxygenase-2 and suppression of platelet surface adhesion.
Insights
Estrogen and raloxifene treatments significantly reduce arterial thrombosis in ovariectomized mice. Both therapies attenuated intravascular thrombosis by increasing cyclooxygenase-2 and decreasing platelet adhesion.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Pharmacology
Background:
- Arterial thrombosis is a significant health concern, and the role of estrogen and selective estrogen receptor modulators (SERMs) in its regulation is not fully understood.
- Ovariectomy in female mice leads to accelerated arterial thrombosis, highlighting the protective effects of endogenous estrogen.
Purpose of the Study:
- To investigate the effects of estradiol and raloxifene on arterial thrombosis and related homeostatic pathways in ovariectomized mice.
- To elucidate the mechanisms underlying the potential antithrombotic effects of estrogen and raloxifene.
Main Methods:
- Ovariectomy or sham surgery was performed on female mice, followed by treatment with estradiol, raloxifene, or placebo for 4 months.
- Arterial thrombosis was induced via photochemical injury in the carotid artery, and the time to vascular occlusion was measured.
- Bone mineral density, uterine atrophy, cyclooxygenase-2 (COX-2) expression, endothelial nitric oxide synthase (eNOS) expression, and platelet adhesion were assessed.
Main Results:
- Ovariectomized mice exhibited accelerated thrombosis compared to sham-operated controls.
- Both estradiol and raloxifene significantly prolonged the time to vascular occlusion, indicating an antithrombotic effect.
- Treatments increased bone mineral density, and both estradiol and raloxifene upregulated COX-2 expression and reduced platelet adhesion, while eNOS expression remained unchanged.
Conclusions:
- Ovariectomy exacerbates arterial thrombosis, while both estradiol and raloxifene demonstrate significant antithrombotic properties.
- The antithrombotic effects are associated with increased COX-2 expression and reduced platelet adhesion.
- Estrogen and raloxifene represent potential therapeutic strategies for managing arterial thrombosis in postmenopausal women.
