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- W2602396445 abstract "Oxidative stress is a hallmark of chronic non-communicable diseases such as arterial hypertension, coronary artery disease, diabetes, and chronic renal disease. Cardiovascular diseases are characterized by increased production of reactive oxygen species (ROS) by NAPDH oxidase 1 (Nox1) and additional Nox isoforms among other sources. Activation of the G protein-coupled estrogen receptor (GPER) can mediate multiple salutary effects on the cardiovascular system. However, GPER also has constitutive activity, e.g. in the absence of specific agonists, that was recently shown to promote hypertension and aging-induced tissue damage by promoting Nox1-derived production of ROS. Furthermore, the small molecule GPER blocker (GRB) G36 reduces blood pressure and vascular ROS production by selectively down-regulating Nox1 expression. These unexpected findings revealed GRBs as first in class Nox downregulators capable to selectively reduce the increased expression and activity of Nox1 in disease conditions. Here, we will discuss the paradigm shift from selective GPER activation to ligand-independent, constitutive GPER signaling as a key regulator of Nox-derived oxidative stress, and the surprising identification of GRBs as the first Nox downregulators for the treatment of chronic non-communicable diseases." @default.
- W2602396445 created "2017-04-07" @default.
- W2602396445 creator A5017376737 @default.
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- W2602396445 date "2018-02-01" @default.
- W2602396445 modified "2023-10-17" @default.
- W2602396445 title "GPER blockers as Nox downregulators: A new drug class to target chronic non-communicable diseases" @default.
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- W2602396445 doi "https://doi.org/10.1016/j.jsbmb.2017.03.019" @default.
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