Sex dimorphism in the cardiovascular responses to d-galactose-induced accelerated aging: effects of HO-1 modulation

Chronic d-galactose (d-gal) injection is an experimental model of accelerated aging in rodents. However, the cardiovascular phenotypes of this model have been poorly characterized, especially as they relate to sex differences. The goal of this study was to investigate the cardiovascular effects of chronic d-gal injection in male and female C57BL/6 mice and the impact of HO-1 induction or inhibition in this model. Forty-eight 8-week-old male and female C57BL/6 mice were divided randomly into four groups (n = 6): control, d-gal, d-gal + CoPP, and d-gal + ZnBG. Body weight, echocardiography, blood pressure measurement, Doppler ultrasound, echoMRI, micro-CT, histopathology, and protein analysis were performed. Our results show a strong sexual dimorphism in the cardiovascular effects of d-gal treatment and the effects of HO-1 induction or inhibition. Male mice were found to be more prone to systolic dysfunction and oxidative stress upon d-gal treatment and benefited more from the protective effects of HO-1 induction. Female mice were found to be protected from the cardiac effects of d-gal treatment yet were more prone to the effects of HO-1 inhibition. Our results demonstrate a sexually dimorphic response to the cardiovascular effects of d-gal treatment and alterations in HO-1.