Estrogen effects on vascular inflammation are age dependent: role of estrogen receptors.
Arterioscler Thromb Vasc Biol
; 34(7): 1477-1485, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24876352
ABSTRACT
OBJECTIVE:
17ß-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. APPROACH ANDRESULTS:
Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pretreatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pretreatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER) knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERß. BMMs derived from aged (versus young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice.CONCLUSIONS:
E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
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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Inflamação
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Macrófagos
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Anti-Inflamatórios
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Músculo Liso Vascular
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article