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

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. (Arterioscler Thromb Vasc Biol. 2005;25:1-5.)