Journal article
Estrogen Protects Against Intracranial Aneurysm Rupture in Ovariectomized Mice
Hypertension (Dallas, Tex. 1979), Vol.63(6), pp.1339-1344
2014
DOI: 10.1161/HYPERTENSIONAHA.114.03300
PMCID: PMC4034536
PMID: 24732889
Abstract
Clinical observations suggest that postmenopausal women have a higher incidence of aneurysmal rupture than premenopausal women. We hypothesize that a relative deficiency in estrogen may increase the risks of aneurysmal growth and subarachnoid hemorrhage in postmenopausal women. We assessed the effects of estrogen and selective estrogen receptor subtype agonists on the development of aneurysmal rupture in ovariectomized female mice. We used an intracranial aneurysm mouse model that recapitulates the key features of human intracranial aneurysms, including spontaneous rupture. Ten- to 12-week-old ovariectomized female mice received treatment with estrogen, nonselective estrogen receptor antagonist, estrogen receptor-α agonist, or estrogen receptor-β agonist starting 6 days after aneurysm induction so that the treatments affected the development of aneurysmal rupture without affecting aneurysmal formation. Estrogen significantly reduced the incidence of ruptured aneurysms and rupture rates in ovariectomized mice. Nonselective estrogen receptor antagonist abolished the protective effect of estrogen. Although estrogen receptor-α agonist did not affect the incidence of ruptured aneurysms or rupture rates, estrogen receptor-β agonist prevented aneurysmal rupture without affecting the formation of aneurysms. The protective role of estrogen receptor-β agonist was abolished by the inhibition of nitric oxide synthase. We showed that estrogen prevented aneurysmal rupture in ovariectomized female mice. The protective effect of estrogen seemed to occur through the activation of estrogen receptor-β, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries.
Details
- Title: Subtitle
- Estrogen Protects Against Intracranial Aneurysm Rupture in Ovariectomized Mice
- Creators
- Yoshiteru TADA - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesKosuke WADA - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesDavid M HASAN - Department of Neurosurgery, University of Iowa, United StatesYasuhisa KANEMATSU - Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, JapanShinji NAGAHIRO - Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, JapanTomoki HASHIMOTO - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesKenji SHIMADA - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesHiroshi MAKINO - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesElena I LIANG - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesShoko MURAKAMI - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesMari KUDO - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesFumiaki SHIKATA - Department of Anesthesia and Perioperative Care, University of California, San Francisco, United StatesRicardo A PENA SILVA - Department of Neurosurgery, University of Iowa, United StatesKeiko T KITAZATO - Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.63(6), pp.1339-1344
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/HYPERTENSIONAHA.114.03300
- PMID
- 24732889
- PMCID
- PMC4034536
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurosurgery; Otolaryngology
- Record Identifier
- 9984040337702771
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