title: Unliganded estrogen receptor alpha regulates vascular cell function and gene expression.
abstract: The unliganded form of the estrogen receptor is generally thought to be inactive. Our prior studies, however, suggested that unliganded estrogen receptor alpha (ERα) exacerbates adverse vascular injury responses in mice. Here, we show that the presence of unliganded ERα decreases vascular endothelial cell (EC) migration and proliferation, increases smooth muscle cell (SMC) proliferation, and increases inflammatory responses in cultured ECs and SMCs. Unliganded ERα also regulates many genes in vascular ECs and mouse aorta. Activation of ERα by E2 reverses the cell physiological effects of unliganded ERα, and promotes gene regulatory effects that are predicted to counter the effects of unliganded ERα. These results reveal that the unliganded form of ERα is not inert, but significantly impacts gene expression and physiology of vascular cells. Furthermore, they indicate that the cardiovascular protective effects of estrogen may be connected to its ability to counteract these effects of unliganded ERα.
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA. Electronic address: gschnitzler@tuftsmedicalcenter.org.
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Schnitzler
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Vallaster
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Erdkamp
authors.affiliation: Tufts Center for Neuroscience Research, Neuroscience Department, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Briggs
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Lakshmanan K
authors.initials: LK
authors.lastname: Iyer
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Iris Z
authors.initials: IZ
authors.lastname: Jaffe
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA. Electronic address: richard.karas@gmail.com.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol
keywords: Cell proliferation; Estrogen receptor alpha; Gene regulation; Vascular injury