Estrogen Receptors Act in Atherosclerosis

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Science's STKE  14 Dec 2004:
Vol. 2004, Issue 263, pp. tw450
DOI: 10.1126/stke.2632004tw450


Men experience a more rapid progression of atherosclerosis, but the basis for this gender difference has not been clear. The prostacyclin PGI2 prevents many processes associated with the formation of atherosclerotic lesions, and the atheroprotective effect of estrogen in women may be via stimulation of PGI2 production. Egan et al. (see the news story by Couzin) now show in a mouse model of atherosclerosis that estrogen acts through the estrogen receptor subtype α to generate PGI2 through cyclooxygenase 2 (COX-2). Female mice lacking a receptor for PGI2 developed atherosclerosis as rapidly as male mice and had poor response to estrogen therapy. This mechanism may be important in assessing the effects of hormone replacement therapy and selective COX-2 inhibitors.

K. M. Egan, J. A. Lawson, S. Fries, B. Koller, D. J. Rader, E. M. Smyth, G. A. FitzGerald, COX-2-derived prostacyclin confers atheroprotection on female mice. Science 306, 1954-1957 (2004). [Abstract] [Full Text]

J. Couzin, Estrogen's ties to COX-2 may explain heart disease gender gap. Science 306, 1277 (2004). [Summary] [Full Text]

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