Chronic GPER activation prevents ischemia/reperfusion injury in ovariectomized rats

IBAÑEZ A; GONZÁLEZ ARBELÁEZ LF; CIOCCI PARDO, A; MOSCA SM; LOFEUDO JM; VELEZ RUEDA JO; AIELLO A; DE GIUSTI VC

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2022

0304-4165

During menopause women are exposed to an increase in cardiovascular risk. G protein-coupled estrogenreceptor (GPER) is known to mediate several of the protective effects of such hormones. G1 was describedas a selective and synthetic agonist for GPER. The aim of the present research is to evaluate the effect of achronic treatment with G1 in ovariectomized (OVX) rats exposed to ischemia/reperfusion (I/R). Consideringthe hypothesis that an impaired mitochondrial state could be involved in the alterations produced in OVXrats, other objective of this study was to investigate it in an isolated preparation. Three months old ratswere assigned to undergo either bilateral ovariectomy or sham operation. The OVX rats were randomlytreated during one month with either G1 or vehicle. Cardiac mitochondria from OVX rats showed adepolarized membrane potential and a decreased calcium retention capacity in comparison with Sham rats,which were prevented by chronic G1 treatment. I/R caused a higher decrease of left ventricular developedpressure and a higher increase of left ventricular end diastolic pressure in OVX compared to Sham hearts.These altered mechanical parameters were prevented by G1. The induced infarct size was significantlyhigher in OVX, which was reduced by G1 treatment. These results indicate that the mitochondrial state inOVX rats is impaired, accompanied by an altered mechanical response after ischemia and reperfusioninjury, which was effectively prevented with chronic treatment with G1. The present study may providefurther insights for the potential development of a therapy based on the GPER modulation.