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Current research project

Title / Titel Molecular mechanisms of estrogen-mediated vascular protection
PDF Abstract (PDF, 14 KB)
Original title / Originaltitel Molekulare Mechanismen Oestrogen-vermittelter Gefässprotektion
Summary / Zusammenfassung Despite the clear-cut gender differences in the morbidity of atherosclerosis in the first five decades of life the imporant role of estrogens for the development of atherosclerosis has recently been subject of much controversy. This controversy is due to the negative results of prospective randomized clinical studies including HERS I, HERS II, and WHI, in which postmenopausal women with and without coronary artery disease were treated during years with so-called “conjugated equine” estrogens and the synthetic progestin medroxyprogesterone acetate. Equine estrogens contain more than 30 different subtances, including testosteron and steroids of unknown activity. At the time of inclusion of the study Patients were many years (decades) after menopause and received very high doses of hormones. The recent identification of new targets of sex hormones, including new estrogen receptors and receptor subtypes and the lack of knowledge about their function and regulation indicates that the issue of hormone treatment is far more complex than previously thought. In this project is aimed to identify mechanisms involved in the cardiovascular protective effects of natural sex steroids and to clarify the role of sex steroid receptors in the cardiovascular system in health and disease, particularly that of the novel G protein-coupled intracellular transmembrane estrogen receptor gpER.

Supported by SNSF grants Nr. 58 421, Nr. 58 426, Nr. 108 258 and Nr. 122 504
Weitere Informationen
Publications / Publikationen Role of GPER in estrogen-dependent nitric oxide formation and vasodilation.
N.C. Fredette, M.R. Meyer, E.R Prossnitz
J Steroid Biochem Mol Biol 76, 65-72, 2018

GPER blockers as Nox downregulators: a new drug class to target chronic non-communicable diseases
M.R. Meyer, M. Barton
J Steroid Biochem Mol Biol 176, 82-87, 2018

Twenty years of G protein-coupled estrogen receptor GPER: historical and personal perspectives
M. Barton, E. J. Filardo, S.J. Lolait, P. Thomas, M. Maggiolini, E.R. Prossnitz
J Steroid Biochem Mol Biol 176, 4-15, 2018

Rapid vasodilation to raloxifene: role of estrogen receptors and off-target effects
M. Barton, E.R. Prossnitz.
Br J Pharmacol 174, 4201-4202, 2017

GPER mediates functional endothelial aging in renal arteries
M.R. Meyer, T. Rosemann, M. Barton, E.R. Prossnitz.
Pharmacology 100, 188-193, 2017

Obligatory role for GPER in cardiovascular aging and disease
M.R. Meyer, N.C. Fredette, C. Daniel, G. Sharma, K. Amann, J.B. Arterburn, M. Barton, E.R. Prossnitz.
Science Signaling 9, ra105, 2016

Estrogen signaling in the adrenal cortex: implications for blood pressure sex differences
T. Carrocia, T.M. Seccia, M. Barton, G.P. Rossi
Hypertension 86, 840-848, 2016

Estrogens and coronary artery disease: new clinical perspectives
M.R. Meyer, M. Barton
Adv Pharmacol 77, 307-360, 2016

GPER is required for the age-dependent upregulation of the myocardial endothelin system
M.R. Meyer, N.C. Fredette, G. Sharma, M. Barton, E.R. Prossnitz
Life Sci 159, 61-65, 2016

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER
M. Barton
Steroids 111, 37-45, 2016

Emerging roles of GPER in diabetes and atherosclerosis

M. Barton, E.R. Prossnitz

Trends Endocrinol Metab 26, 185-192, 2015

G protein-coupled estrogen receptor inhibits vascular prostanoid production and activity
M.R. Meyer, N.C. Fredette, M. Barton, E.R. Prossnitz
J Endocrinol 227, 61-69, 2015

Nicolaus Copernicus and the rapid vascular responses to aldosterone
M. Barton, M.R. Meyer
Trends Endocrinol Metab 26, 396-398, 2015

G Protein-coupled estrogen receptor protects from atherosclerosis
M. R. Meyer, N.C. Fredette, T.A. Howard, C. Hu, C. Ramesh, C. Daniel, K. Ammann, J.B. Arterburn, M. Barton, E.R. Prossnitz.
Sci Rep 4, 7564, 2014

Estrogen biology: New insights on GPER function and clinical opportunities
E.R. Prossnitz, M. Barton
Mol Cell Endocrinol 389, 71-83, 2014

Alike but not the same: Anatomic heterogeneity of estrogen receptor- mediated vasodilation

M. Barton, M.R. Meyer, E.R Prossnitz
J Cardiovasc Pharmacol 62, 22-25, 2013

Mechanisms and therapy of atherosclerosis and its clinical complications

M. Barton
Curr Opin Pharmacol 13, 149-153, 2013

Cholesterol and atherosclerosis: Modulation by estrogen
M. Barton
Curr Opin Lipidol 24, 214-220, 2013

GPER regulates endothelin-dependent vascular tone and intracellular calcium

M.R. Meyer, A.S. Field, N.L. Kanagy, M. Barton, E.R. Prossnitz
Life Sci 91, 623-627, 2012

Testosterone and secondary hypertension: New pieces to the puzzle
M. Barton, E.R. Prossnitz, M.R. Meyer
Hypertension 59, 1011-1103, 2012

Position paper: The membrane estrogen receptor GPER - Clues and questions
M. Barton
Steroids 77, 935-942, 2012

Deletion of the G protein-coupled estrogen receptor increases endothelial vasoconstriction
M.R. Meyer, K. Amann, A.S. Field, C. Hu, H.J. Hathyway, N.L. Kanagy, M.K. Walker, M. Barton, E.R. Prossnitz
Hypertension 59, 507-512, 2012

GPER regulates endothelin-dependent vascular tone and intracellular calcium
M.R. Meyer, A.S. Field, N.L. Kanagy, M. Barton, E.R. Prossnitz
Life Sci epub Feb 2, 2012

The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function
M.R. Meyer, E.R. Prossnitz, M. Barton
Vascul Pharmacol 55, 17-25, 2011

The G protein-coupled estrogen receptor GPER in physiology and disease
E.R. Prossnitz, M. Barton
Nature Rev Endocrinol 7, 715-726, 2011

Estrogen-independent activation of estrogen receptors
M. Barton, M.R. Meyer, E.R. Prossnitz
Hypertension 57, 1056-1057, 2011

GPER/GPR30 and regulation of vascular tone and blood pressure
M.R. Meyer, E.R. Prossnitz, M. Barton
Immunol Endocr Metab Agents Med Chem 4, 255-261, 2011

Obesity, insulin resistance and diabetes: sex differences and role of estrogens receptors
M.R. Meyer, D.J. Clegg, E.R. Prossnitz, M. Barton
Acta Physiol (Oxf) 203, 259-269, 2011

Estrogen-independent activation of estrogen receptors
M. Barton, M.R. Meyer, E.R. Prossnitz.
Hypertension 57, 1056-1057, 2011

Dilation of epicardial coronary arteries by the G protein-coupled estrogen receptor agonists G-1 and ICI 182,780
M.R. Meyer, O. Baretella, E.R. Prossnitz, M. Barton.
Pharmacology 86, 58-64, 2010

Lung cancer and hormone replacement therapy.
M. Barton, M.R. Meyer, J.L. Bolton, E.R.Prossnitz.
Lancet 375 (9709), 117-118, 2010

ERα, ERβ, and gpER: Novel aspects of estrogen receptor signaling in atherosclerosis
M.R. Meyer, M. Barton.
Cardiovasc Res 83, 605-610, 2009

Signaling, physiological functions and clinical relevance of the G protein-coupled estrogen
receptor GPER
E.R. Prossnitz, M. Barton.
Prostaglandins Other Lipid Mediat 89, 89-97, 2009

Postmenopausal hypertension: Mechanisms and therapy
M. Barton, M.R. Meyer.
Hypertension 54, 11-18, 2009

Non-genomic regulation of vascular cell function and growth by estrogen.
M. Barton, E. Haas, E.R. Prossnitz, M.R. Meyer.
Mol Cell Endocrinol 308, 9-16, 2009

Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity
E. Haas, I. Bhattacharya, E. Brailoiu, M. Damjanovic, G.C. Brailoiu, X. Gao, L. Mueller-Guerre, A. Gut, R. Minotti, M.R. Meyer, K. Amann, E. Ammann, A. Perez-Dominguez, M. Genoni, D.J. Clegg, N.J. Dun, T.C. Resta, E.R. Prossnitz, M. Barton.
Circ Res 104, 288-291, 2009 (rapid report).

Need for research on estrogen receptor function: Importance for hormone replacement therapy and atherosclerosis
M.R. Meyer, E. Haas, M. Barton.
Gend Med 5, S10-S22, 2008

Differential effects of 17β-estradiol on function and expression of ERα, ERβ, and GPR30 in arteries and veins of patients with atherosclerosis
E. Haas, M.R. Meyer, U. Schurr,I. Bhattacharya, R. Minotti, H.H. Nguyen, A. Heigl, M.Lachat, M. Genoni, M. Barton
Hypertension 49, 1358-63, 2007

Distinct roles of estrogen receptors alpha and beta mediating acute vasodilatation of epicardial coronary arteries.
T. Traupe, C. D. Stettler, H. Li, E. Haas, I. Bhattacharya, R. Minotti, M. Barton
Hypertension 49, 1364-70, 2007

Hormone replacement therapy and atherosclerosis in postmenopausal women: Does aging limit therapeutic benefits?
M. Barton, M.R. Meyer, E. Haas.
Arterioscler Thromb Vasc Biol 27, 1669-1672, 2007

Gender differences of cardiovascular disease: New perspectives for estrogen receptor signaling
M.R. Meyer, E. Haas, M. Barton
Hypertension 47, 1019-1026, 2006

Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen.
R. K. Dubey, B. Imthurn, M. Barton, E.K. Jackson
Cardiovasc Res 66, 295- 306, 2005

Aging and biomedicine 2005: Where should we go from here?
M. Barton.
Cardiovasc Res 66, 187-189, 2005

Postmenopausal hormone-replacement therapy.
M. Barton, Dubey, R.K.
New Engl J Med 346, 63-65, 2002

Weitere Informationen

Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. Matthias Barton (Project Leader)
Dr. Matthias Meyer  
Dr. Oliver Baretella  
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung), Foundation, Others
In collaboration with /
In Zusammenarbeit mit
Prof. H. Li, University of Mainz Germany
Prof. E. Prossnitz, University of New Mexico United States
Prof. M. Genoni, Triemlispital Zürich Switzerland
Duration of Project / Projektdauer Jun 2005 to Dec 2020