Increased carbamylation level of HDL in end-stage renal disease: carbamylated-HDL attenuated endothelial cell function

Am J Physiol Renal Physiol. 2016 Mar 15;310(6):F511-7. doi: 10.1152/ajprenal.00508.2015. Epub 2016 Jan 13.

Abstract

It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. The present study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy control subjects (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using ELISA. Isolated C-HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells were treated with C-HDL or native HDL to assess their migration, proliferation, and angiogenesis properties. HDL-associated paraoxonase 1 activity was also determined by spectrophotometry assay. Compared with healthy control subjects, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis, and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated paraoxonase 1 activity was decreased and negatively correlated with the carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of VEGF receptor 2 and scavenger receptor class B type I signaling pathways in endothelial cells. In conclusion, the present study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair functions.

Keywords: carbamylation; end-stage renal disease; endothelial repair; high-density lipoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aryldialkylphosphatase / metabolism
  • Case-Control Studies
  • Cyanates / metabolism
  • Endothelial Cells / physiology*
  • Female
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / etiology
  • Lipoproteins, HDL / metabolism*
  • Male
  • Middle Aged
  • Scavenger Receptors, Class B / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Cyanates
  • Lipoproteins, HDL
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Aryldialkylphosphatase
  • PON1 protein, human