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Canadian Journal of Cardiology

Mechanisms of Estrogen Effects on the Endothelium: An Overview

  • Subhadeep Chakrabarti
    Affiliations
    Department of Obstetrics and Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
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  • Jude S. Morton
    Affiliations
    Department of Obstetrics and Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
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  • Sandra T. Davidge
    Correspondence
    Corresponding author: Dr Sandra T. Davidge, 232 HMRC, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Tel.: +1-780-492-8562; fax: +1-780-492-1308.
    Affiliations
    Department of Obstetrics and Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada

    Department of Physiology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
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Published:November 18, 2013DOI:https://doi.org/10.1016/j.cjca.2013.08.006

      Abstract

      In this review, we aim to provide an overview of the recent advances in understanding estrogen effects on the vascular endothelium. Epidemiological studies suggest the female sex hormone estrogen mediates the relative protection of premenopausal women against cardiovascular disease, compared with age-matched men. However, results from clinical trials of exogenous estrogen supplementation in postmenopausal women have been disappointing, generating much controversy about the role of estrogen and demonstrating the need for further research in this field. Here we have discussed the roles of different estrogen receptors (ERs) such as ERα, ERβ, and G-protein coupled receptor 30; the complex genomic and nongenomic signalling pathways downstream to ER activation and the factors such as age, menopause, pregnancy, and diabetes that might alter estrogen responses. The common themes of this discussion are the complexity and diversity of endothelial estrogen responses and their modulation by 1 or more coexisting factors. Finally, we summarize the emerging therapeutic options including improved targeting of individual ERs and signalling pathways that might maximize the therapeutic potential of estrogenic compounds while minimizing their harmful side effects.

      Résumé

      Dans cette revue, notre voulons donner un aperçu des récents progrès en matière de compréhension des effets de l'œstrogène sur l'endothélium vasculaire. Les études épidémiologiques montrent que l'œstrogène, une hormone sexuelle femelle, intervient dans la protection relative des femmes préménopausées contre la maladie cardiovasculaire comparativement aux hommes appariés selon l'âge. Cependant, les résultats des essais cliniques sur la supplémentation en œstrogènes exogènes chez les femmes postménopausées se sont avérés décevants, suscitant une importante controverse sur le rôle de l'œstrogène et démontrant la nécessité de réaliser d'autres recherches dans ce domaine. Ici, nous avons discuté des rôles des différents récepteurs des œstrogènes (ER : estrogen receptor) comme le ERα, le ERβ et le récepteur 30 couplé aux protéines G; les voies de signalisation génomique et non génomique complexe en aval de l'activation des ER et les facteurs comme l'âge, la ménopause, la grossesse et le diabète qui pourraient modifier les réponses aux œstrogènes. Les thèmes communs de cette discussion sont la complexité et la diversité des réponses de l'endothélium aux œstrogènes et leur modulation par 1 facteur coexistant ou plus. Finalement, nous résumons les options thérapeutiques émergentes incluant l'amélioration du ciblage individuel des RO et des voies de signalisation qui pourraient maximiser le potentiel thérapeutique des composantes œstrogéniques tout en minimisant leurs effets secondaires dangereux.
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