G protein-coupled estrogen receptor GPR30 exerts vasoprotective effects in apolipoprotein E-deficient mice

Introduction GPR30 is an intracellular transmembrane G protein-coupled receptor that mediates non-genomic estrogen signaling. The agonist G-1 modulates glucose homeostasis and vascular function. However, its impact on inflammation atherogenesis has not yet been investigated in the atherosclerotic apolipoprotein E-deficient(ApoE-/-) mouse model. Material methods ApoE-/- mice were fed a high-cholesterol diet for 7 weeks while being treated with selective (n=6-7). After treatment period, relaxation capacity, oxidative stress, plaque burden assessed. In vitro, reactive oxygen species, expression levels of angiotensin II type1(AT1) receptor, proliferation rate quantified human coronary artery smooth muscle cells(HCASMC). Results significantly improved tolerance vivo (142.2±8.1mg/dl vs. 204.6±13.3mg/dl), reduced stress (221±88RLU/s/mg vs.1,983±885RLU/s/mg) endothelium-dependent vasodilation (relaxation to 35.1±4.5% vs.63.0±4.6%). Furthermore, female (56.5±3.7% vs.75.5±2.9%). provoked significant downregulation AT1 HCASMC (0.67±0.09-fold). blunted II-induced ROS production by (817±7RLU/s/mg vs.1,625±105 RLU/s/mg) diminished (-26.8±2.7% vs.+50.4±1.7%). Conclusions Selective activation improves decreases vitro vivo. antioxidant effect might be mediated receptor. vivo, associated endothelial function ApoE-deficient mice, indicating beneficial effects activation. agonism thus compelling strategy against atherosclerosis.