IGF-1 mediates cardiac and cognitive improvement in exercised ovariectomized rats

IBAÑEZ, ALEJANDRO; MARTINEZ, VALERIA; GODOY COTO, JOSHUA; VELEZ RUEDA, JORGE OMAR; LOFEUDO, JUAN MANUEL; CERVELLINI, SOFIA; ECHAVARRIA, LILA; BELLINI, MARIA JOSE; DOLCETTI, FRANCO JUAN CRUZ; PORTIANSKI, ENRIQUE; YEVES, ALEJANDRA; ENNIS, IRENE; AIELLO, ERNESTO ALEJANDRO; DE GIUSTI, VERÓNICA

La Plata

Congreso; Annual Metting of ISHR Latinamerica; 2022

International Society of Heart Research

During menopause women are exposed to an increase in cardiovascular risk (CVR), associated with lack ofestrogens. However classic hormone replacement therapy has not been as successful as expected inpreventing such pathologies. Sodium/proton exchanger (NHE) and Sodium/bicarbonate cotransporter (NBC)are regulators of the cardiomyocyte pH. NHE hyperactivity and the reduced activity of the electrogenicisoform of NBC (NBCe1) are correlated with increased CVR. Estrogen deficiency is associated with cognitivechanges and exploratory behavior. Aerobic exercise exerts beneficial effects on cardiovascular health andcognitive processes, and Insulin like growth factor 1 (IGF1) is a mediator of these effects.Bilateral ovariectomy was performed in young female Wistar rats (OVX). OVX rats were randomly assigned toa sedentary group (OVX s ) or to an aerobic swimming routine (8 weeks/5 days a week) (OVX e ). Another group ofOVX rats were intramuscularly injected with a recombinant adenoviral construct harboring the cDNA ofhuman IGF-1 (RAd-IGF1). OVX s cardiomyocytes were cultured and treated with IGF1 (1uM) to measure theimpact in ROS production.Aerobic training induces physiological hypertrophy in OVX e . NHE activity was increased in OVX s , and bothexercise and Rad-IGF1 injection abolished this alteration. NBCe1 activity was decreased in OVX s , and exerciseprevented it. Antioxidant capacity was impaired in OVX s , and recovered after the training. OVX IGF1 rats showedan improvement in long-term memory and exploratory behavior, both of which were affected by ovariectomy.IGF1 decreased ROS production in OVX s cultured cardiomyocytes.Our results show that aerobic training has a positive impact in the remodeling of alkalinizing mechanismsobserved in OVX s , as well as an increase in antioxidant capacity, and this is, at least partially, due to IGF1signaling. Our data also support the involvement of sex hormones in cognitive functions in female rats andsuggest a positive effect of transgenic IGF1.