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• W1145404920 endingPage "320" @default.
• W1145404920 startingPage "309" @default.
• W1145404920 abstract "We have provided evidence that the stimulatory effects of (−)-epicatechin ((−)-EPI) on endothelial cell nitric oxide (NO) production may involve the participation of a cell-surface receptor. Thus far, such entity(ies) has not been fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell-surface receptor that has been linked to protective effects on the cardiovascular system and activation of intracellular signaling pathways (including NO production) similar to those reported with (−)-EPI. In bovine coronary artery endothelial cells (BCAEC) by the use of confocal imaging, we evidence the presence of GPER at the cell-surface and on F-actin filaments. Using in silico studies we document the favorable binding mode between (−)-EPI and GPER. Such binding is comparable to that of the GPER agonist, G1. By the use of selective blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (−)-EPI is dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We also evidence by the use of siRNA the role that GPER has on mediating ERK1/2 activation by (−)-EPI. GPER appears to be coupled to a non Gαi/o or Gαs, protein subtype. To extrapolate our findings to an ex vivo model, we employed phenylephrine pre-contracted aortic rings evidencing that (−)-EPI can mediate vasodilation through GPER activation. In conclusion, we provide evidence that suggests the GPER as a potential mediator of (−)-EPI effects and highlights the important role that GPER may have on cardiovascular system protection." @default.
• W1145404920 created "2016-06-24" @default.
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• W1145404920 date "2015-10-01" @default.
• W1145404920 modified "2023-10-17" @default.
• W1145404920 title "The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)" @default.
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• W1145404920 doi "https://doi.org/10.1016/j.phrs.2015.08.014" @default.
• W1145404920 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4555879" @default.
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