Effects of estrogen on the vascular injury response in estrogen receptor α,β (double) knockout mice

Richard H. Karas, Henny Schulten, Gary Pare, Mark J. Aronovitz, Claes Ohlsson, Jan Ake Gustafsson, Michael E. Mendelsohn

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

The two known estrogen receptors, ERα and ERβ, 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), ERα knockout (ERαKOCH), and ERβ knockout (ERβKOCH) mice. We generated mice harboring disruptions of both ERα and ERβ genes (ERα,βKOCH) by breeding and studied the effect of 17β-estradiol (E2) on vascular injury responses in ovariectomized female ERα,βKOCH mice and WT littermates. E2 inhibited increases in vascular medial area following injury in the WT mice but not in the ERα,βKOCH 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 ERα,βKOCH mice. These data support that the role of estrogen receptors differs for specific components of the vascular injury response in the ERα,βKOCH mice. The results leave unresolved whether E2 inhibition of VSMC proliferation in ERα,βKOCH mice is caused by a receptor-independent mechanism, an unidentified receptor responsive to estrogen, or residual activity of the ERα splice variant reported previously in the parental ERαKOCH mice. These possibilities may be resolved by studies of mice in which ERα has been fully disrupted (ERαKOSt), which are in progress.

Original languageEnglish (US)
Pages (from-to)534-539
Number of pages6
JournalCirculation Research
Volume89
Issue number6
DOIs
StatePublished - Sep 14 2001

Keywords

  • 17β-estradiol
  • Animal models
  • Hormone action
  • Vascular injury

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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