title: Endothelial estrogen receptor isoforms and cardiovascular disease.
abstract: Rapid, nongenomic vascular cell and tissue responses to estrogen have been demonstrated for more than a decade. Although the pendulum continues to swing, accumulating evidence, both clinical and pre-clinical, support favorable effects of ovarian steroid hormones in the vascular system. These effects are mediated both by classical steroid hormone receptor-mediated transcriptional modulation, and largely by endothelial plasma membrane-associated estrogen receptor (ER)α, which when engaged triggers a signaling cascade resulting in release of cardioprotective nitric oxide (NO). In addition to full-length ERα (ER66), an N-terminus truncated ERα isoform, ER46, plays a key role in these rapid endothelial responses to 17β-estradiol (E2). We have recently determined that ER46 can be a Type I integral transmembrane molecule. In this review, we discuss ER isoforms, rapid E2-stimulated signaling in the endothelium, the importance of the ER46 transmembrane orientation, and the clinical context of this rapid endothelial signaling.
authors: Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA.
authors: Kyung Hee
authors: KH
authors: Kim
authors: Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA.
authors: Bryan D
authors: BD
authors: Young
authors: Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA. Electronic address: jeffrey.bender@yale.edu.
authors: Jeffrey R
authors: JR
authors: Bender
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D020033:Protein Isoforms; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004967:Estrogens; D020033:Protein Isoforms; D011960:Receptors, Estrogen
keywords: ER46; Endothelium; Estrogen; eNOS