Abstract P112: Sex Differences and the Role of G Protein-Coupled Estrogen Receptor in Arterial Stiffening

Abstract

Pulse wave velocity (PWV) independently predicts cardiovascular events and is exacerbated in women following menopause. Since our previous work shows that G protein-coupled estrogen receptor (GPER) plays a protective role in the vasculature, the current study evaluated sex differences and the impact of GPER on arterial stiffening. We hypothesized that genetic deletion of GPER attenuates sex differences in arterial stiffness. Male and female wildtype (wt) and global GPER knockout (ko) mice (n=46) were used between 16-21 weeks of age. Ang II infusion (700 ng/kg/day for two weeks) was used to induce hypertension, and SBP was measured using tail cuff plethysmography. Local PWV within the carotid artery was obtained via high frequency ultrasound in both color Doppler and M-mode. The excised carotid was subjected to passive biaxial mechanical testing followed by four fiber family constitutive modeling. Statistical analysis was performed using two-way ANOVA with Sidak’s multiple comparisons test. Baseline SBP was significantly lower in females (P=0.035) but was not impacted by genotype. Baseline PWV was significantly higher in male versus female wt mice (P<0.01) but was not different in ko mice. Baseline axial (P<0.01) and circumferential (P=0.027) stiffness was higher in female wt mice but was not impacted by genotype. Ang II infusion significantly increased SBP (P<0.001) and PWV (P<0.001) in all groups, removing any impact of sex or genotype. Ang II increased axial stiffness and decreased diagonal collagen in male and female GPER ko mice. In conclusion, we found that GPER deletion did not impact blood pressure but removed sex differences in PWV. While female wt mice had the lowest PWV at baseline, genetic deletion of GPER or Ang II infusion removed this protection independent of BP. Therefore, local carotid PWV may provide information on vascular status independent of BP, and GPER plays an important role in vascular compliance and arterial stiffening.