SuO003ANGIOPOIETIN-2 ACCELERATES VASCULAR CALCIFICATION IN CHILDREN WITH CHRONIC KIDNEY DISEASE UNDERGOING DIALYSIS

Abstract

Introduction and Aims: Cardiovascular disease (CVD), manifested by vascular calcification, is the primary cause of mortality in paediatric patients with chronic kidney disease (CKD). One of the earliest signs of CVD is endothelial dysfunction; this may occur due to the imbalance of vascular growth factors observed in CKD. We have previously shown that circulating levels of angiopoietin-2 (Angpt-2) - a pro-inflammatory and anti-angiogenic molecule - were dramatically increased in paediatric dialysis patients. However, whether Angpt-2 actively drives vascular calcification or is simply a marker of altered angiogenesis is yet to be established. Method(s): Muscular arteries were obtained from children undergoing renal transplantation and non-renal patients undergoing intra-abdominal surgery. 1-2 mm wide arterial rings, as well as explanted vascular smooth muscle cells (VSCMs), were cultured in high calcium and phosphate (Ca+P) milieu with/without 25 ng/ml of Angpt-2, the highest concentration measured previously in dialysis serum. Calcium content for both vessels and cells were measured after 14 days and 5 days respectively. Result(s): Arterial rings from healthy paediatric controls and pre-dialysis CKD patients did not calcify when exposed to Ca+P media with/without Angpt-2. In contrast, arterial rings from dialysis patients showed increase calcium content, which was significantly enhanced with the addition of Angpt-2 (p=0.04). Total VSMC number in the tunica media remained consistent between vessels stimulated with pro-calcaemic media, with and without Angpt-2 as assessed by number of nuclei present. Similarly, cells explanted from the tunica media of dialysis patients also exhibited a significantly increased calcium load following exposure to pro-calcaemic media and Angpt-2. The presence of the angiopoietin receptor, Tie-2, was detected by immunohistochemistry andWestern blotting on vessel rings and cultured dialysis cells respectively. Conclusion(s): Angpt-2 accelerated vascular calcification in vessel rings and cultured cells obtained from children with CKD undergoing dialysis, and this effect may potentially mediated through Tie-2. Modulation of angiopoietins to slow vascular calcification in CKD patients requires further study.