Circulation Research. 2001;89:534-539
Published online before print August 30, 2001, doi: 10.1161/hh1801.097239
Published online before print August 30, 2001, doi: 10.1161/hh1801.097239
© 2001 American Heart Association, Inc.
Integrative Physiology |
Effects of Estrogen on the Vascular Injury Response in Estrogen Receptor 
,ß (Double) Knockout Mice
From the Molecular Cardiology Research Institute, Department of Medicine (R.H.K., H.S., G.P., M.J.A., M.E.M.), and Division of Cardiology, New England Medical Center Hospitals and Tufts University School of Medicine, Boston, Mass; Department of Internal Medicine (C.O.), Sahlgrenska University Hospital, Gothenburg, Sweden; and Department of Medical Nutrition (J.-A.G.), Karolinska Institute, NOVUM, Huddinge, Sweden.
Correspondence to Michael E. Mendelsohn, MD, Tufts University School of Medicine, New England Medical Center, Molecular Cardiology Research Institute, 750 Washington St, Box 80, Boston, MA 02111. E-mail mmendelsohn{at}lifespan.org
Abstract — The two known estrogen receptors, ER
and ERß, mediate the effects of estrogen in all target tissues, including blood vessels. We have shown previously that estrogen inhibits vascular injury response to the same extent in female wild-type (WT), ER knockout (ERKOCH), and ERß knockout (ERßKOCH) mice. We generated mice harboring disruptions of both ER and ERß genes (ER,ßKOCH) by breeding and studied the effect of 17ß-estradiol (E2) on vascular injury responses in ovariectomized female ER,ßKOCH mice and WT littermates. E2 inhibited increases in vascular medial area following injury in the WT mice but not in the ER,ßKOCH mice, demonstrating for the first time that the two known estrogen receptors are necessary and sufficient to mediate estrogen inhibition of a component of the vascular injury response. Surprisingly, as in WT littermates, E2 still significantly increased uterine weight and inhibited vascular smooth muscle cell (VSMC) proliferation following injury in the ER,ßKOCH mice. These data support that the role of estrogen receptors differs for specific components of the vascular injury response in the ER,ßKOCH mice. The results leave unresolved whether E2 inhibition of VSMC proliferation in ER,ßKOCH mice is caused by a receptor-independent mechanism, an unidentified receptor responsive to estrogen, or residual activity of the ER splice variant reported previously in the parental ERKOCH mice. These possibilities may be resolved by studies of mice in which ER has been fully disrupted (ERKOSt), which are in progress.
Key Words: animal models • vascular injury • 17ß-estradiol • hormone action
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