Figure 5. A small molecule GPER-selective agonist inhibits atherosclerosis and vascular inflammation.

Treatment effects on atherosclerosis (a), uterine wet weight (b) or quantification of CD68+ (c), (e), (f) and CD3+ (d)–(f) staining of macrophages and T cells, respectively, in the aortic root. Data were obtained in ovariectomized (surgically postmenopausal) gper+/+ mice, which display accelerated atherogenesis (cf. Fig 1a–d). Effects are shown in response to treatment with placebo (filled bars) or G-1 (hatched bars), a selective small molecule agonist of GPER. G-1 treatment reduced atherosclerosis by 45% (a). Ovariectomy reduced uterine weight by about 90% compared with ovary-intact animals (b), in which estrogen levels are high. G-1 treatment had no feminizing effect on the uterus similar to placebo treatment (b). G-1 treatment reduced staining for CD68+ cells by 43% (c), (e), (f), but had no effect on CD3+ immunostaining (d)–(f). *P < 0.05 compared with placebo, ***P < 0.001 compared with ovary intact (Student's t-test). All data (n = 5–11 per group) are mean ± s.e.m. Scale bar, 100 μm.