Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation.
Arterioscler Thromb Vasc Biol
; 37(6): 1127-1137, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28473445
ABSTRACT
OBJECTIVE:
Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17ß-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro. APPROACH ANDRESULTS:
Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERß]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus independently of plaque growth or lipid levels and occurred in association with a site-specific decrease in the proportion of ERß-positive intimal cells. Calcified lesions expressed collagen I and bone sialoprotein, with decreased matrix Gla protein. In vitro, E2 suppressed ERß expression and increased VSMC mineralization, demonstrating increased collagen I and II, osteocalcin and bone sialoprotein, and reduced matrix Gla protein and osteopontin. Antagonism or RNA silencing of estrogen receptor alpha, ERß, or both further increased VSMC mineralization.CONCLUSIONS:
We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERß activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Diferenciação Celular
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Miócitos de Músculo Liso
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Receptor alfa de Estrogênio
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Receptor beta de Estrogênio
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Estradiol
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Aterosclerose
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Calcificação Vascular
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article