on January 20, 2005
Published online before print January 20, 2005, doi: 10.1161/01.ATV.0000156536.89752.8e
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Submitted on September 15, 2004
Accepted on December 28, 2004
Modulation of Estrogen Signaling by the Novel Interaction of Heat Shock Protein 27, a Biomarker for Atherosclerosis, and Estrogen Receptor 
. Mechanistic Insight Into the Vascular Effects of Estrogens
Harvey Miller ;
From University of Ottawa Heart Institute, Ontario, Canada.
* To whom correspondence should be addressed. E-mail: eobrien{at}ottawaheart.ca.
Objective--We sought to discover proteins that associate with estrogen receptor beta (ER
) and modulate estrogen signaling.
Methods and Result--Using a yeast 2-hybrid screen, we identified heat shock protein 27 (HSP27) as an ER-associated protein. HSP27 is a recently identified biomarker of atherosclerosis that is secreted at reduced levels from atherosclerotic compared with normal arteries. In vitro protein-binding assays confirmed the specific interaction of HSP27 with ER and not ER
. HSP27 expression was absent in coronary arteries with complex atherosclerotic lesions. Interestingly, HSP27 expression was also absent in 60% of coronary arteries from young males and females (27±6.5 years) with normal histology or nonobstructive fatty streaks/atheromas. Moreover, the absence of HSP27 in these normal or minimally diseased arteries coincided with the loss of ER expression. Only 35% of arteries showed coexpression of HSP27 and ER. Relative to controls, estradiol-mediated transcription was reduced 20% with overexpression of HSP27 and increased 44% when HSP27 protein levels were reduced with HSP27 siRNA.
Conclusions--HSP27, an ER-associated protein, shows attenuated expression with coronary atherosclerosis and modulates estrogen signaling.
Key words: atherosclerosis • hormones • receptors • signal transduction • women
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