Activation of the GPR30 receptor inhibits aldosterone-induced cardiac hypertrophy

DI MATTÍA RA; AIELLO EA; ORLOWSKI A

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Introduction: GPR30 was first described as a membrane orphan G protein-coupled receptor. Later it was demonstrated that estrogen can act as a receptor ligand. It has been reported that the activation of GPR30 is cardioprotective. The administration of its synthetic ligand G1 reduced the infarct size in ischemia-reperfusion, attenuated heart failure and induced a decrease in perivascular fibrosis. The steroid hormone aldosterone (Ald) plays a classic role acting through mineralocorticoid receptor (MR) and its activation on the cardiovascular system generates cardiac hypertrophy, fibrosis and heart failure. It has been recently proposed that certain non-genomic effects of Ald are due to the activation of GPR30. However these results are in contraposition with the beneficial effects of GPR30 activation. Objetives: The aim of this work was to evaluate the role of GPR30 activation in both in vitro and in vivo models of cardiac hypertrophy. Materials and methods: We cultured neonatal rat cardiomyocytes (NRCM) from 1-3 days Wistar rats and treated them for 48 hours with Ald (10nM), G1 (1uM) or the co mbination of both. Furthermore, we transfected NRCM with siRNAs against MR (siMR) and GPR30 (siGPR30) and treated another group with MR inhibitor Eplerenone (Eple) 10µM. Then we examined simultaneous treatment with Ald (10nM) for 48 hours in all these groups.Our in vivo model consisted of three months old Spontaneous Hypertensive Rats (SHR) treated with G1 administered with osmotic mini pumps for 28 days. We performed echocardiography and evaluated cardiac hypertrophy parameters. Results: Hypertrophy caused by Ald was attenuated by the co-treatment with G1 (cellular area % respect to control,Control:1±0.07,n=9;Ald:1.33±0.05*,n=8;Ald+G1:0.93±0.05,n=7;*p