The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima Development Through a Direct Effect on Smooth Muscle Cells

Circulation Research
Natalia SmirnovaJean-François Arnal

Abstract

17β-Estradiol (E2) exerts numerous beneficial effects in vascular disease. It regulates gene transcription through nuclear estrogen receptor α (ERα) via 2 activation functions, AF1 and AF2, and can also activate membrane ERα. The role of E2 on the endothelium relies on membrane ERα activation, but the molecular mechanisms of its action on vascular smooth muscle cells (VSMCs) are not fully understood. The aim of this study was to determine which cellular target and which ERα subfunction are involved in the preventive action of E2 on neointimal hyperplasia. To trigger neointimal hyperplasia of VSMC, we used a mouse model of femoral arterial injury. Cre-Lox models were used to distinguish between the endothelial- and the VSMC-specific actions of E2. The molecular mechanisms underlying the role of E2 were further characterized using both selective ERα agonists and transgenic mice in which the ERαAF1 function had been specifically invalidated. We found that (1) the selective inactivation of ERα in VSMC abrogates the neointimal hyperplasia protection induced by E2, whereas inactivation of endothelial and hematopoietic ERα has no effect; (2) the selective activation of membrane ERα does not prevent neointimal hyperplasia; and (3) ERαA...Continue Reading

References

Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·R H KarasM E Mendelsohn
Nov 25, 2000·Journal of the American College of Cardiology·B Chandrasekar, J F Tanguay
Jun 1, 2002·Circulation Research·Gary PareMichael E Mendelsohn
Feb 11, 2004·Endocrine Reviews·Carolyn L Smith, Bert W O'Malley
Apr 10, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·David MankaIan J Sarembock
May 4, 2005·Circulation·Marco A Costa, Daniel I Simon
Mar 14, 2007·Circulation·John E DeanfieldTon J Rabelink
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maria Cristina AntalManuel Mark
Mar 14, 2008·Current Drug Targets·David Y Hui
Oct 23, 2008·Genesis : the Journal of Genetics and Development·Olivia WendlingDaniel Metzger
Jan 31, 2009·Circulation Research·Elvira HaasMatthias Barton
Feb 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Audrey Billon-GalésJean-François Arnal
Dec 26, 2009·Steroids·Gernot LangerChristiane Otto
Dec 15, 2010·Endocrine-related Cancer·Leigh C MurphyPeter H Watson
Feb 24, 2011·The Journal of Biological Chemistry·Qian WuPhilip W Shaul
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Audrey Billon-GalésJean-François Arnal
Nov 22, 2011·The Journal of Surgical Research·Melissa E HoggMelina R Kibbe
May 15, 2013·The American Journal of Pathology·Coralie FontaineJean-François Arnal
Dec 29, 2013·Proceedings of the National Academy of Sciences of the United States of America·Marine AdlanmeriniFrançoise Lenfant
Jul 31, 2014·The Journal of Experimental Medicine·Natalia F SmirnovaMuriel Laffargue

❮ Previous
Next ❯

Citations

Feb 4, 2016·Circulation Research·Sara Menazza, Elizabeth Murphy
Jun 5, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Ryuta UmezuKensuke Egashira
May 8, 2020·International Journal of Molecular Sciences·Coralie FontaineBarbara Garmy-Susini
Jun 21, 2020·International Journal of Molecular Sciences·Laila AryanMansoureh Eghbali
Oct 17, 2018·Current Drug Targets·Angeles C Tecalco-CruzEduardo Cruz-Ramos
Apr 26, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Kailin YangJinwen Ge
Oct 6, 2020·Circulation Research·Rana ZahreddineCoralie Fontaine
Nov 19, 2021·Endocrine Reviews·Franck Mauvais-JarvisEllis R Levin

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
dissection
Nuclear Magnetic Resonance

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.