In vivo evaluation by optical and PET imaging of IP angiogenesis and validation of PFKFB3 inhibitors in a murine vein graft model Baganha F.1, De Vries M1. and Quax P.1 1Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden Atherosclerosis is a disease of the medium and large arteries in which fatty lesions called atheromatous plaques grows on the inner surfaces of the arterial walls. In Europe, it’s responsible for 4 million annual deaths and for 90% of cardiovascular disease cases. This way, the stability of atherosclerotic plaques is determinant for acute clinical implications and between all the factors associated with this phenotype, angiogenesis has shown up as a major one. The angiogenic neovessels that grow in the intraplaque region are immature and inherently leaky, permitting inflammatory cell infiltration and influx of blood constituents into the plaque. Without a mature endothelial and pericyte layer, those neovessels promote the entry of leukocytes and erythrocytes into to plaque leading to inflammatory activating and intraplaque hemorrhage, respectively. During the formation of a new vessels, the sprouting of the endothelial cells is glucose driven. In the glycolytic flux, the conversion of fructose-6-phosphate (F-6-P) to fructose-2,6-bisphosphate (F-2,6-P2) is a rate-limiting checkpoint and it is modulated by PFKFB enzymes. As a result, PFKFB plays a crucial role in maintaining glucose homeostasis. Using vein graft surgery in male ApoE3 Leiden mice, we investigated if PFKFB3 inhibition can stop the intraplaque angiogenesis and if PFKFB3 can be a target in atherosclerosis treatment.