Details

Autor(en) / Beteiligte

• Pare, Gary
• Krust, Andrée
• Karas, Richard H
• Dupont, Sonia
• Aronovitz, Mark
• Chambon, Pierre
• Mendelsohn, Michael E

Titel

Estrogen Receptor-α Mediates the Protective Effects of Estrogen Against Vascular Injury

Ist Teil von

• Circulation research, 2002-05, Vol.90 (10), p.1087-1092

Ort / Verlag

Hagerstown, MD: American Heart Association, Inc

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Blood vessel cells express the 2 known estrogen receptors, α and β (ERα, ERβ), which are thought to mediate estrogen inhibition of vascular injury and atherosclerosis, but the relative role of ERα and ERβ in these events is controversial. Estrogen inhibits the vascular injury response to the same extent in ovariectomized female wild-type mice and in the original single gene knockout mice for ERα (ERαKOChapel Hill [ERαKOCH]) and ERβ (ERβKOChapel Hill [ERβKOCH]). In double gene knockout mice generated by crossing these animals (ERα,βKOCH), estrogen no longer inhibits medial thickening after vascular injury, but still inhibits vascular smooth muscle cell proliferation and increases uterine weight. The partial retention of estrogen responsiveness in ERα,βKOCH mice could be due either to the presence of a novel, unidentified estrogen receptor or to functional expression of an estrogen receptor-α splice variant in the parental ERαKOCH mice. To distinguish between these possibilities, we studied recently generated mice fully null for estrogen receptor α (ERαKOStrasbourg [ERαKOSt]) and examined the effect of estrogen on the response to vascular injury. In the present study, we show that after vascular injury in ovariectomized ERαKOSt mice, estrogen has no detectable effect on any measure of vascular injury, including medial area, proteoglycan deposition, or smooth muscle cell proliferation. These data demonstrate that estrogen receptor-α mediates the protective effects of estrogen on the response to vascular injury.