Chronic GPER activation prevents ischemia/reperfusion injury in ovariectomized rats

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 2; p. 130060
• Main Authors: Ibañez, Alejandro Martin, González Arbeláez, Luisa Fernanda, Ciocci Pardo, Alejandro, Mosca, Susana, Lofeudo, Juan Manuel, Velez Rueda, Jorge Omar, Aiello, Ernesto Alejandro, De Giusti, Verónica Celeste
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2022
• Subjects: Animals; Calcium - metabolism; Cardioprotection; Female; GPER; Ischemia/reperfusion injury; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria, Heart - metabolism; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Ovariectomized rats; Ovariectomy; Rats; Rats, Wistar; Receptors, Estrogen - metabolism; Receptors, G-Protein-Coupled - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Mitochondria; Ischemia/reperfusion injury; Cardioprotection; Ovariectomized rats; GPER
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2021.130060

During menopause women are exposed to an increase in cardiovascular risk. G protein-coupled estrogen receptor (GPER) is known to mediate several of the protective effects of such hormones. G1 was described as a selective and synthetic agonist for GPER. The aim of the present research is to evaluate the effect of a chronic treatment with G1 in ovariectomized (OVX) rats exposed to ischemia/reperfusion (I/R). Considering the hypothesis that an impaired mitochondrial state could be involved in the alterations produced in OVX rats, other objective of this study was to investigate it in an isolated preparation. Three months old rats were assigned to undergo either bilateral ovariectomy or sham operation. The OVX rats were randomly treated during one month with either G1 or vehicle. Cardiac mitochondria from OVX rats showed a depolarized 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 developed pressure 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 significantly higher in OVX, which was reduced by G1 treatment. These results indicate that the mitochondrial state in OVX rats is impaired, accompanied by an altered mechanical response after ischemia and reperfusion injury, which was effectively prevented with chronic treatment with G1. The present study may provide further insights for the potential development of a therapy based on the GPER modulation.
•Mitochondrial state of OVX rats is impaired and chronic G1 administration prevents it.•The mechanical response after I/R injury is altered in ovariectomized rats.•The infarct size after I/R injury is higher in ovariectomized rats.•The chronic treatment with G1 improves myocardial mechanical response in OVX rats.•The chronic treatment with G1 reduces the infarct size in OVX rats.