Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis

PLoS One. 2013;8(2):e56273. doi: 10.1371/journal.pone.0056273. Epub 2013 Feb 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiopoietin-2 / blood*
  • Angiopoietin-2 / metabolism
  • Arteries / metabolism
  • Arteries / pathology
  • Biomarkers / blood
  • Cardiovascular Diseases / complications*
  • Cell Adhesion Molecules / blood
  • Cell Adhesion Molecules / chemistry
  • Child
  • Female
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Male
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / pathology
  • Renal Insufficiency, Chronic / therapy*
  • Solubility
  • Time Factors
  • Uric Acid / pharmacology
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Angiopoietin-2
  • Biomarkers
  • Cell Adhesion Molecules
  • Vascular Endothelial Growth Factor A
  • Uric Acid
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1