title: Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis.
abstract: Cardiovascular disease (CVD) is increasingly recognised as a complication of childhood chronic kidney disease (CKD) even in the absence of diabetes and hypertension. We hypothesized that an alteration in angiopoietin-1 and -2, growth factors which regulate endothelial and vascular function could be involved. We report that the endothelial survival factor, angiopoietin-1 is low in children with pre-dialysis CKD whereas the pro-inflammatory angiopoietin-2 is elevated in children on dialysis. In dialysis patients, angiopoietin-2 positively correlated with time on dialysis, systolic blood pressure, and carotid artery intima media thickness. Elevated angiopoietin-2 levels in dialysis versus pre-dialysis CKD patients were also associated with an anti-angiogenic (high soluble VEGFR-1 and low VEGF-A) and pro-inflammatory (high urate, E-selectin, P-selectin and VCAM-1) milieu. Ang-2 was immunodetected in arterial biopsy samples whilst the expression of VEGF-A was significantly downregulated in dialysis patients. Serum urate correlated with angiopoietin-2 levels in dialysis patients and addition of uric acid was able to induce rapid release of angiopoietin-2 from cultured endothelial cells. Thus, angiopoietin-2 is a marker for cardiovascular disease in children on chronic dialysis and may act as an anti-angiogenic and pro-inflammatory effector in this context. The possibility that the release of angiopoietin-2 from endothelia is mediated by urate should be explored further.
authors: Nephro-Urology Unit, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
authors: Rukshana C
authors: RC
authors: Shroff
authors: Karen L
authors: KL
authors: Price
authors: Maria
authors: M
authors: Kolatsi-Joannou
authors: Alexandra F
authors: AF
authors: Todd
authors: David
authors: D
authors: Wells
authors: John
authors: J
authors: Deanfield
authors: Richard J
authors: RJ
authors: Johnson
authors: Lesley
authors: L
authors: Rees
authors: Adrian S
authors: AS
authors: Woolf
authors: David A
authors: DA
authors: Long
mesh_terms: D000293:Adolescent; D042702:Angiopoietin-2 / Q000097:blood* / Q000378:metabolism; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000150:complications*; D015815:Cell Adhesion Molecules / Q000097:blood / Q000737:chemistry; D002648:Child; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D012995:Solubility; D013997:Time Factors; D014527:Uric Acid / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D042461:Vascular Endothelial Growth Factor A; D014527:Uric Acid; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1