Prof. Dr. med. Georg Nickenig
Medical Clinic II for Cardiology, Angiology and Pneumology
georg.nickenig@ukbonn.de View member: Prof. Dr. med. Georg Nickenig
Archives of medical science : AMS
INTRODUCTION: GPR30 is an intracellular transmembrane G protein-coupled receptor that mediates non-genomic estrogen signaling. The GPR30 agonist G-1 modulates glucose homeostasis and vascular function. However, its impact on vascular inflammation and atherogenesis has not yet been investigated in the atherosclerotic apolipoprotein E-deficient (ApoE) mouse model.
MATERIAL AND METHODS: ApoE mice were fed a high-cholesterol diet for 7 weeks while being treated with the selective GPR30 agonist G-1 ( = 6-7 per sex and treatment group). After the treatment period, vascular relaxation capacity, vascular oxidative stress, and atherosclerotic plaque burden were assessed. , reactive oxygen species, expression levels of the angiotensin II type 1 (AT) receptor, and the proliferation rate were quantified in human coronary artery smooth muscle cells (HCASMC).
RESULTS: G-1 significantly improved glucose tolerance (142.2 ±8.1 mg/dl vs. 204.6 ±13.3 mg/dl), reduced vascular oxidative stress (221 ±88 RLU/s/mg vs. 1,983 ±885 RLU/s/mg), and improved endothelium-dependent vasodilation (relaxation to 35.1 ±4.5% vs. 63.0 ±4.6%). Furthermore, treatment with G-1 significantly reduced the atherosclerotic plaque burden of female ApoE mice (56.5 ±3.7% vs. 75.5 ±2.9%). , G-1 significantly downregulated the AT receptor in HCASMC (0.67 ±0.09-fold). Furthermore, G-1 blunted angiotensin II-induced ROS production in HCASMC (817 ±7 RLU/s/mg vs. 1,625 ±105 RLU/s/mg) and diminished HCASMC proliferation (-26.8 ±2.7% vs. +50.4 ±1.7%).
CONCLUSIONS: Selective GPR30 activation improves glucose tolerance and decreases vascular ROS production and , the antioxidant effect might be mediated by downregulation of the AT receptor. , the antioxidant effect of G-1 is associated with improved endothelial function and reduced atherosclerotic plaque burden in ApoE-deficient mice, indicating beneficial vascular effects of GPR30 activation. GPR30 agonism may therefore represent a promising therapeutic strategy against atherosclerosis.
Copyright: © 2021 Termedia & Banach.
PMID: 42877180