RESUMO
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 AND RESULTS: 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.
Assuntos
Anti-Inflamatórios/farmacologia , Estradiol/farmacologia , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fatores Etários , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Lesões das Artérias Carótidas/imunologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Células Cultivadas , Modelos Animais de Doenças , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Neointima , RNA Mensageiro/metabolismo , Receptores de Estrogênio , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: Uterine rupture after endometrial ablation is rare and has not been reported previously in the English literature. CASE: A 33-year-old multigravida at 26 5/7 weeks of gestation had undergone two endometrial ablation procedures. The first attempt 2 years before pregnancy was complicated by uterine perforation. She presented with severe abdominal pain. A cesarean delivery was performed for recurrent late fetal heart rate deceleration, and a complete spontaneous uterine rupture was discovered. CONCLUSION: Pregnancies that occur after endometrial ablation have a risk of morbidity. Physicians must counsel women on the importance of contraception or sterilization as a critical component of the procedure.
