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

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. This study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy controls (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using enzyme-linked immunosorbent assay (ELISA). Isolated carbamylated HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells (HAECs) were treated with C-HDL or native HDL to assess their migration, proliferation and angiogenesis properties. HDL-associated paraoxonase1 (PON1) activity was also determined by spectrophotometry assay. Compared with healthy controls, 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 PON1 activity was decreased and negatively correlated with carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and scavenger receptor class B type I (SR-BI) signaling pathways in endothelial cells. In conclusion, this study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair function.