17β-estradiol, aging, inflammation, and the stress response in the female heart

James P. Stice, Le Chen, Se Chan Kim, J. S. Jung, A. L. Tran, T. T. Liu, Anne A Knowlton

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Heat shock proteins (HSPs) are a cardioprotective class of proteins induced by stress and regulated by the transcription factor, heat shock factor (HSF)-1. 17β-estradiol (E2) indirectly regulates HSP expression through rapid activation of nuclear factor-κB (NF-κB) and HSF-1 and protects against hypoxia. As males experience a loss of protective cellular responses in aging, we hypothesized that aged menopausal (old ovariectomized) rats would have an impaired HSP response, which could be prevented by immediate in vivo E2 replacement. After measuring cardiac function in vivo, cardiac myocytes were isolated from ovariectomized adult and old rats with and without 9 weeks of E2 replacement. Myocytes were treated with E2 in vitro and analyzed for activation of NF-κB, HSF-1, and HSP expression. In addition, we measured inflammatory cytokine expression and susceptibility to hypoxia/reoxygenation injury. Cardiac contractility was reduced in old ovariectomized rats and could prevented by immediate E2 replacement in vivo. Subsequent investigations in isolated cardiac myocytes found that in vitro E2 activated NF-κB, HSF-1, and increased HSP 72 expression in adult but not old rats. In response to hypoxia/reoxygenation, myocytes from adult, but not old, rats had increased HSP 72 expression. In addition, expression of the inflammatory cytokines TNF-α and IL-1β, as well as oxidative stress, were increased in myocytes from old ovariectomized rats; only the change in cytokine expression could be attenuated by in vivo E2 replacement. This study demonstrates that while aging in female rats led to a loss of the cardioprotective HSP response, E2 retains its protective cellular properties.

Original languageEnglish (US)
Pages (from-to)1589-1598
Number of pages10
JournalEndocrinology
Volume152
Issue number4
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Endocrinology

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    Stice, J. P., Chen, L., Kim, S. C., Jung, J. S., Tran, A. L., Liu, T. T., & Knowlton, A. A. (2011). 17β-estradiol, aging, inflammation, and the stress response in the female heart. Endocrinology, 152(4), 1589-1598. https://doi.org/10.1210/en.2010-0627