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Estrogen inhibits the vascular injury response in estrogen receptor α-deficient mice

Nature Medicine volume 3, pages 545–548 (1997)Cite this article

Abstract

The atheroprotective effects of estrogen in women are well recognized1, but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ERα (ref. 2—6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions78. We have generated mice in which the ERα gene is disrupted9 and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17β-estradiol. Suprisingly, in both wild-type and estrogen receptor-deficient mice, 17β-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular injury by a novel mechanism that is independent of the classic estrogen receptor, ERα.

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Author information

Authors and Affiliations

  1. Molecular Cardiology Research Center, New England Medical Center, Tupper Research Institute, 750 Washington Street, Boston, Massachusetts, 02111, USA

    Mark D. Iafrati, Richard H. Karas, Mark Aronovitz, Sung Kim, Theodore R. Sullivan Jr., Thomas F. O'Donnell Jr. & Michael E. Mendelsohn

  2. Departments of Biochemistry and Child Health, University of Missouri, Columbia, Missouri, 65201, USA

    Dennis B. Lubahn

  3. Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences NIH, Research Triangle Park, North Carolina, 27709, USA

    Kenneth S. Korach

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Iafrati, M., Karas, R., Aronovitz, M. et al. Estrogen inhibits the vascular injury response in estrogen receptor α-deficient mice. Nat Med 3, 545–548 (1997). https://doi.org/10.1038/nm0597-545

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