The activation of the G protein-coupled estrogen receptor (GPER) prevents and regresses cardiac hypertrophy

DI MATTIA RA; PORTIANSKY EL; ORLOWSKI A; BLANCO PG; AIELLO EA; MARIÁNGELO JI; MUNDIÑA-WEILENMANN CB

Rosario

Congreso; Reunión anual de la Sociedad Argentina de Fisiología (SAFIS); 2019

Introduction: The G protein-coupled estrogen receptor (GPER) has been associated to non-genomic actions of estrogen inthe heart. The activation of GPER by its synthetic ligand G1 has been shown to be cardioprotective. Thus, the aim of thiswork was to evaluate the role of GPER activation in both in vitro and in vivo models of cardiac hypertrophy.Experimental design: For the in vitro model, neonatal rat cardiomyocytes (NRCM) were treated for 48 hours withAldosterone (Ald), G1, or the combination of both. The mineralocorticoid receptor (MR) and the GPER were blocked bypharmacological and molecular tools (transfecting cells with specific siRNAs). Cell area was measured in all cases. The in vivomodel consisted of Spontaneous Hypertensive Rats (SHR) treated with G1, administered with osmotic mini pumps for 28days. Echocardiographic studies were performed and evaluation of cardiac hypertrophy parameters was assessed.Results: In NRCM, the hypertrophy induced by Ald was prevented by the co-treatment with G1. Both, the reduction of theexpression of MR by the siRNA and the MR blocker, eplerenona, totally prevented the hypertrophic effect of Ald in NRCM. Inaddition, G1 was unable to prevent Ald-induced hypertrophy when the cells were transfected with siGPER or treated with itssynthetic antagonists, G15 and G36. Echocardiographic studies showed a reduced left ventricular mass index in SHR treatedduring 28 days with G1 (normalized by tibia length in mg/cm; Wistar: 250.8±15.75, n=5; SHR*: 376.5±16.67, n=6; SHR Veh*:377.3±20.93, n=6; SHR G1: 263.4±41.52, n=7; *p