For example, GPR81 knockdown in a breast cancer cell line suppressed VEGF (vascular endothelial growth factor) and amphiregulin, retarding angiogenesis.14 Similarly, in the sensorimotor cortex of GPR81 knockout mice (Gpr81−/−), the induction of VEGF-A and increased capillary density by either treadmill exercise or subcutaneous lactate injections was absent.16 Ex vivo lactate infusion in the rat retina decreases capillary lumen diameter,17 suggesting vasomotor effects of GPR81 activation. This evidence concerns the gene HCAR1 and breast carcinoma.