ArticleCirculation research2015
The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima Development Through a Direct Effect on Smooth Muscle Cells.
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Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
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Who cites it
32 citing papers in PubMed, 62 citations in OpenAlex.
- Postmenopausal osteoporosis and vascular calcification: The estrogen regulation network and calcification paradox.Journal of translational internal medicine · 2026Article
- Sexually dimorphic role of estrogen receptor α in preserving right ventricular endothelial integrity.bioRxiv : the preprint server for biology · 2025Article
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Overexpression of adipose tissue ERα enhances PVAT anticontractility via NOX4-derived HAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Estrogen Inhibits the Phenotypic Switching of Vascular Smooth Muscle Cells through ER-α/CREB in Aortic Dissection.ACS omega · 2025Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia.Cellular and molecular life sciences : CMLS · 2024Article
- Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth.Theranostics · 2024Article
- Sex differences and related estrogenic effects in heart failure with preserved ejection fraction.Heart failure reviews · 2023Review
- Estetrol: From Preclinical to Clinical Pharmacology and Advances in the Understanding of the Molecular Mechanism of Action.Drugs in R&D · 2023Review
- The different natural estrogens promote endothelial healing through distinct cell targets.JCI insight · 2023Article
- Tie2-Cre-Induced Inactivation of Non-Nuclear Estrogen Receptor-α Signaling Abrogates Estrogen Protection Against Vascular Injury.JACC. Basic to translational science · 2023Article
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Role of estrogen receptors in health and disease.Frontiers in endocrinology · 2022Review
- Article
- Estetrol: A New Choice for Contraception.Journal of clinical medicine · 2021Review
- Estrogen Receptor and Vascular Aging.Frontiers in aging · 2021Review
- 17Mediators of inflammation · 2021Article
- Proteolysis-targeting chimeras and their implications in breast cancer.Exploration of targeted anti-tumor therapy · 2021Review
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Authors and funding
16 authors at 1 institution in 1 country.
Natalia F SmirnovaFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Coralie FontaineFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Mélissa BuscatoFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Adrien LupieriFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Alexia VinelFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Marie-Cécile ValeraFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Maeva GuillaumeFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Nicole MaletFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Jean-Michel FoidartFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Isabelle Raymond-LetronFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Francoise LenfantFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Pierre GourdyFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Benita S KatzenellenbogenFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
John A KatzenellenbogenFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Muriel LaffargueFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Jean-Francois ArnalFrom the Department of Vascular Biology of the Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France (N.F.S., C.F., M.B., A.L., A.V., M.-C.V., M.G., N.M., F.L., P.G., M.L., J.-F.A.); Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Université de Liège, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Liège, Belgique (J.-M.F.); UMR INRA/DGER 1225, Université de Toulouse, INP, ENVT, Toulouse, France (I.R.-L.); Departments of Molecular and Integrative Biology (B.S.K.) and Chemistry, University of Illinois at Urbana-Champaign (J.A.K.).
Inserm · FR
Funding
Pharmacokinetics, Bioavailability, and Metabolism/Daniel R. DoergeP50AT006268 · NCCIH · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI HELFERICH, WILLIAM G · 2010 to 2015
$7.6MNovel Ligands and Mechanisms to Achieve Selective Nuclear Receptor ActivityR01DK015556 · NIDDK · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI KATZENELLENBOGEN, JOHN A. · 1986 to 2016
$1.6MNCCIH NIH HHS P50 AT006268NCCIH NIH HHS P50AT006268NIDDK NIH HHS R01 DK015556NIDDK NIH HHS R01DK015556
Abstract
rationale17β-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.
objectiveThe 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. METHODS AND
resultsTo 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) ERαAF1 is necessary and sufficient to inhibit postinjury VSMC proliferation.
conclusionsAltogether, ERαAF1-mediated nuclear action is both necessary and sufficient to inhibit postinjury arterial VSMC proliferation, whereas membrane ERα largely regulates the endothelial functions of E2. This highlights the exquisite cell/tissue-specific actions of the ERα subfunctions and helps to delineate the spectrum of action of selective ER modulators.
Indexed as
ActinsAnimalsArteriesCell MembraneCell NucleusCell ProliferationEndothelium, VascularEstradiolEstrogen Receptor alphaEstrogensFemoral ArteryHyperplasiaImmunohistochemistryMice, Inbred C57BLMice, KnockoutMice, TransgenicActinsEstradiolEstrogen Receptor alphaEstrogensPlatelet Endothelial Cell Adhesion Molecule-1estradiolestrogen receptor alphamicemyocytessmooth muscle
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