Abstract P170: Similarities And Differences In The Vascular Impact Of Estrogen Loss Versus G Protein-coupled Estrogen Receptor Deletion

Abstract

Women in their postmenopausal years have an increased risk of cardiovascular disease, and recent research suggests that increased vascular stiffness can be detected within a year of the onset of menopause. We have previously demonstrated that the G Protein-Coupled Estrogen Receptor (GPER) protects the vasculature without noticeable changes in blood pressure, but little is known about the underlying structural changes that provide protection. In this study we assessed the impact of estrogen and the G protein-coupled estrogen receptor (GPER) on vascular health, with the hypothesis that loss of estrogen or deletion of smooth muscle cell (smc)-GPER would similarly increase vascular stiffness. Female mice were separated into three cohorts: intact wildtype, ovariectomized (OVX), and GPER smc-KO. OVX occurred at 8 weeks of age and 8 weeks later blood pressure was measured via tail-cuff plethysmography, arterial stiffness was measured as pulse wave velocity (PWV) via high resolution ultrasound, and carotids were excised for biaxial pressure myography and imaging. Uterine weight in OVX mice (0.03 g) was significantly lower than intact mice (0.1 g; p=0.0002) confirming the loss of estrogen. No difference was observed in systolic blood pressure, however, both the OVX (1.5 m/s) and smc-KO (1.9 m/s) groups had significantly higher PWV than intact controls (1.2 m/s; p=0.02 and p=0.03, respectively). Carotids of OVX (366 μm) and smc-KO (389 μm) mice had a smaller outer diameter versus controls (441 μm; p >0.05) without a difference in thickness. Despite the similar responses of OVX and smc-KO groups, Masson’s trichrome staining of carotid sections showed significantly more smooth muscle area fraction in OVX (p=0.005), but not KO mice, and no difference in collagen area fraction. These data indicate that while estrogen loss and smc-KO of GPER both increase arterial stiffness, increased smooth muscle due to estrogen loss is likely not modulated through GPER. Future experiments will aim to understand how other components, such as extracellular matrix genes, may be affected by loss of GPER.