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Activation of the GPR30 receptor inhibits aldosterone‐induced cardiac hypertrophy
Author(s) -
Orlowski Alejandro,
Di Mattía Romina Alejandra,
Aiello Ernesto Alejandro
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.843.6
Subject(s) - gper , agonist , medicine , endocrinology , chemistry , aldosterone , muscle hypertrophy , receptor , estrogen receptor , cancer , breast cancer
The hormone aldosterone (Ald) plays classic role acting through mineralocorticoids receptors (MR) located in the cytosol, which act as ligand‐induced transcription factors. Many cardiac deleterious effects of Ald are mediated by the activation of the MR. However, activated MR can also elicit additional non‐genomic effects. In addition, it has been recently proposed that certain non‐genomic effects of Ald were due to the activation of the G protein‐coupled receptor 30 (GPR30). It has been reported that the activation of GPR30 is cardioprotective. The administration of the GPR30 synthetic agonist G1 reduced the infarct size, diminished left ventricular wall thickness, attenuated heart failure and induced a decrease in perivascular fibrosis. The aim of this study was to investigate the potential cardioprotective effects of GPR30 on Ald‐induced hypertrophy in neonatal cardiac myocytes. Consistent with previous reports, dose‐dependent response to 24 hs Ald treatment increased cell size (A.U., control: 186±11, n=20; Ald (0.1nM): 185±12, n=22; Ald (1 nM): 202±12, n=17; Ald (10 nM): 260±21*, n=23; Ald (100 nM): 268±17*, n=29; Ald (1000 nM): 275±15*, n=14; * indicates p<0.05), while no significant effects were found with the synthetic agonist of GPR30 (G1) (A.U., control: 186±11, n=20; G1 (0.1 nM): 189±10, n=26; G1 (1 nM): 192±13, n=30; G1(10 nM): 188±7, n=24; G1 (100 nM): 197±11, n=30; G1 (1000 nM): 196±14, n=22). The Ald‐induced hypertrophy was cancelled when the expression of MR was silenced with a small hairpin interference RNA directed against it (A.U., Ald (10nM) + siControl: 419.28±14.19, n=54; Ald(10nM) + siMR: 423.48±14.64, n=62). Interestingly, the Aldo‐induced cell hypertrophy was significantly inhibited with the treatment with G1 (1000 nM), (A.U., control: 524±9, n=96; Ald (10 nM): 737±9, n=93; Ald (10 nM)+G1 (1000 nM): 351±10, n=96; *p<0.05). We examined the intracellular signaling pathways induced by G1 and Ald. The results show that G1 (1000 nM) or G1+Ald (10 nM) incubation increases AKT phosphorylation. However, no significant changes were observed with the incubation with Ald alone. In summary, these results showed that G1 was able to prevent the hypertrophy induced by Ald, indicating that activation of GPR30 prevents the hypertrophy produced by the stimulation of MR induced by the hormone.