Obligatory role for GPER in cardiovascular aging and disease

Meyer MR, Fredette NC, Daniel C, Sharma G, Amann KU, Arterburn JB, Barton M, Prossnitz ER (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Science Signaling American Association for the Advancement of Science

Book Volume: 9

Pages Range: ra105

Journal Issue: 452

DOI: 10.1126/scisignal.aag0240

Abstract

Pharmacological activation of the heptahelical G protein-coupled estrogen receptor (GPER) by selective ligands counteracts multiple aspects of cardiovascular disease. We thus expected that genetic deletion or pharmacological inhibition of GPER would further aggravate such disease states, particularly with age. To the contrary, we found that genetic ablation of Gper in mice prevented cardiovascular pathologies associated with aging by reducing superoxide (?O2(-)) formation by NADPH oxidase (Nox) specifically through reducing the expression of the Nox isoform Nox1 Blocking GPER activity pharmacologically with G36, a synthetic, small-molecule, GPER-selective blocker (GRB), decreased Nox1 abundance and ?O2(-) production to basal amounts in cells exposed to angiotensin II and in mice chronically infused with angiotensin II, reducing arterial hypertension. Thus, this study revealed a role for GPER activity in regulating Nox1 abundance and associated ?O2(-)-mediated structural and functional damage that contributes to disease pathology. Our results indicated that GRBs represent a new class of drugs that can reduce Nox abundance and activity and could be used for the treatment of chronic disease processes involving excessive ?O2(-) formation, including arterial hypertension and heart failure.

Authors with CRIS profile

Christoph Daniel Department of Nephropathology Kerstin Ute Amann Department of Nephropathology

Involved external institutions

University of New Mexico (UNM) / Universidad de Nuevo México US United States (USA) (US) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) New Mexico State University (NMSU) US United States (USA) (US)

How to cite

APA:

Meyer, M.R., Fredette, N.C., Daniel, C., Sharma, G., Amann, K.U., Arterburn, J.B.,... Prossnitz, E.R. (2016). Obligatory role for GPER in cardiovascular aging and disease. Science Signaling, 9(452), ra105. https://doi.org/10.1126/scisignal.aag0240

MLA:

Meyer, Matthias R., et al. "Obligatory role for GPER in cardiovascular aging and disease." Science Signaling 9.452 (2016): ra105.

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