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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-02022018-164722
Document
Author
Full name
Tiago Januário da Costa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Carvalho, Maria Helena Catelli de (President)
Chaves, Maria Luiza Morais Barreto de
D'Avila, Kátia de Angelis Lobo
Munhoz, Carolina Demarchi
Zanesco, Angelina
Title in Portuguese
Influência dos tratamentos com estrógeno, iniciados precoce e tardiamente, em fêmeas com envelhecimento precoce (SAMP8) ou não (SAMR1) ovariectomizadas: estudo do mecanismo  de ação em carótidas.
Keywords in Portuguese
Splicing alternativo
Artéria carótida
Doenças cardiovasculares
Estrógeno
Pós-menopausa
Receptor de estrógeno
Abstract in Portuguese
Ensaios clínicos observacionais e em animais sugerem que o estrógeno exerça proteção cardiovascular, entretanto existem controvérsias mesmo após estudos randomizados. Tem sido sugerido que existe uma janela de oportunidade terapêutica, teoria timing hypothesis, que analisa o tratamento com estrógeno, iniciado precoce ou tardiamente, em mulheres na pós-menopausa. Avaliamos a função de carótidas de camundongos fêmeas com senescência acelerada (SAMP8) ou resistentes (SAMR1) ovariectomizadas tratadas com estrógeno precoce e tardiamente. Em SAMR1 os tratamentos promoveram vasculoproteção e nas carótidas das SAMP8 o tratamento com início precoce não alterou o efeito da ovariectomia, porém o tratamento com início tardio aumentou a vasoconstrição à fenilefrina, a produção de tromboxano (TXA2) e a expressão proteica do ERα-36kDa, splicing alternativo do receptor clássico ERα-66kDa. Portanto, os efeitos do estrógeno não foram benéficos no envelhecimento, podendo contribuir para o desenvolvimento de doenças cerebrovasculares decorrentes de alteração na circulação cerebral.
Title in English
Influence of early and late estrogen treatments in ovariectomized senescence accelerated (SAMP8) and resistant (SAMR1) female mice: a study of the mechanism of action in the carotid.
Keywords in English
Alternative splicing
Cardiovascular disease
Carotid artery
Estrogen
Estrogen receptor
Postmenopause
Abstract in English
Observational clinical trials and animal studies demonstrated that estrogen promote cardiovascular protection. However, there are controversies after randomized clinical trials. It has been suggested that there is a therapeutic window of opportunity timing hypothesis theory , which analyzes the early and late estrogen treatments in postmenopausal women. We evaluated the carotid function in ovariectomized senescence (SAMP8) and resistant (SAMR1) female mice treated with estrogen in mineral oil solution dose of 5 g/kg by subcutaneous injection every three days. In SAMR1 estrogen treatments promoted vasculoprotection. In SAMP8 early-onset estrogen treatment did not change the effect observed in the ovariectomy, however late-onset estrogen treatment increased the vasoconstriction to phenylephrine, the thromboxane production and the protein expression of ERα-36kDa, alternative splicing. Therefore, the effects of estrogen were not beneficial in aging, contributing to the development of cardio and cerebrovascular diseases due to alteration cerebral circulation.
 
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Release Date
2020-02-02
Publishing Date
2018-02-02
 
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