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1551660 
Journal Article 
Estrogen and the cardiovascular system 
Knowlton, AA; Lee, AR 
2012 
1 
Pharmacology and Therapeutics
ISSN: 0163-7258
EISSN: 1879-016X 
135 
1 
54-70 
22484805 
WOS:000305302500005 
Estrogen is a potent steroid with pleiotropic effects,
which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The
rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is
protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much
slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription
factor, both activating and repressing gene expression. Several different ERs regulate the
specificity of response to estrogen, and appear to have specific effects in cardiac remodeling
and the response to injury. However, much remains to be understood about the selectivity of these
receptors and their specific effects on gene expression. Basic studies have demonstrated that
estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen
also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an
anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and
not shown the clear-cut benefit of more basic investigations. This can be explained in part by
differences in study design: in basic studies estrogen treatment was used immediately or shortly
after ovariectomy, while in some key clinical trials, estrogen was given years after menopause.
Further basic research into the underlying molecular mechanisms of estrogen's actions is
essential to provide a better comprehension of the many properties of this powerful hormone.
Published by Elsevier Inc. 
Estrogen; Aging; Cardiovascular; Inflammation; Cardiac hypertrophy; Endothelial; Cardiac myocyte; Heart failure; HRT; Menopause