Published online Apr 26, 2022. doi: 10.4330/wjc.v14.i4.220
Peer-review started: December 10, 2021
First decision: February 15, 2022
Revised: February 17, 2022
Accepted: March 27, 2022
Article in press: March 27, 2022
Published online: April 26, 2022
Processing time: 129 Days and 4 Hours
Different mineralocorticoid receptor (MR) antagonists (MRAs) have different potencies at the cardiac MR blockade. G protein-coupled receptor kinase (GRK)-5 phosphorylates the MR in the heart and inhibits its transcriptional activity.
The authors wanted to compare two different MRAs, eplerenone and finerenone, in their ability to stimulate GRK5-dependent MR inhibition in cardiac myocytes.
The authors sought to identify a mechanism for the increased effectiveness of finerenone over eplerenone at blocking cardiac MR.
The authors studied MR phosphorylation and activity in cardiomyocytes in response to eplerenone or finerenone treatments.
GRK5 is necessary for the anti-apoptotic, anti-oxidative, and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis, oxidative stress, and fibrosis.
Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart.
GRK5 is an essential mediator of finerenone’s effects on cardiac aldosterone antagonism.