Cardiovascular disease (CVD) manifested by calcification is the major cause of mortality in childhood chronic kidney disease (CKD). One of the earliest signs of CVD is endothelial damage and dysfunction which may result from disturbances in growth factors involved in the formation of vascular networks. Our previous work showed that circulating levels of angiopoietin-2 (Angpt2) – a pro-inflammatory and anti-angiogenic molecule – were dramatically increased in children on dialysis and may act as a biomarker for CVD. However, whether Angpt2 directly contributes to the vascular calcification seen in CVD is yet to be established. To examine this, vessel rings from the inferior epigastric artery were obtained from paediatric patients undergoing renal transplantation or intra-abdominal surgery following informed written consent from the child’s guardian. Vessel rings from age-matched healthy controls, pre-dialysis (n=4) and dialysis (n=3) children were cultured in a high calcium and phosphate milieu with/without 25ng/mL of Angpt2, the highest concentration measured in dialysis serum. Vessels from healthy controls and pre-dialysis patients did not calcify when exposed to pro-calcaemic media; in contrast, dialysis vessels showed increased calcium content which was further enhanced in the presence of Angpt2 (Figure), when assessed by cresolphtalein colorometric assay. In addition, cells explanted from the tunica media of dialysis patients exhibited increased calcium deposition as observed through Alizarin red staining in the presence of high calcium and phosphate. Deposition was further exaggerated with the addition of Angpt2. mRNA levels of bone morphogenic protein-2, a pro-osteogenic gene involved in chondrocyte formation, increased in dialysis cells exposed to a pro-calcaemic milieu; these were further enhanced with the addition of Angpt2. In contrast, levels of Matrix-gla protein, an osteogenic inhibitor, were lost with the addition of calcium and phosphate and not altered in cells exposed to Angpt2. Finally, we examined expression of the angiopoietin receptor Tie-2, primarily expressed on endothelial cells, to determine if the effects of Angpt2 on calcification could be mediated through this pathway. Immunostaining of vessel rings revealed prominent localisation of Tie-2 in the tunica media; furthermore, cell explants expressed the receptor by qRT-PCR and Western blotting. In conclusion, we have provided the first evidence that vascular calcification can be modulated by Angpt2 potentially acting through the Tie-2 receptor.