High-density lipoprotein from end-stage renal disease patients exhibits superior cardioprotection and increase in sphingosine-1-phosphate

Research output: Contribution to journalArticle

Abstract

Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine-1-phosphate (S1P), HDL-associated S1P (HDL-S1P) and HDL-mediated protection against oxidative stress between CKD and control patients. Methods: High-density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL-S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin-induced oxidative stress in vitro were measured. Results: Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro-inflammatory cytokines (TNF-alpha and IL-6). Unexpectedly, HDL-S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL-S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively. Discussion: The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL-mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL-S1P.

Details

Authors
  • Jonas W. Brinck
  • Aurélien Thomas
  • Marie Claude Brulhart-Meynet
  • Estelle Lauer
  • Cecilia Frej
  • Björn Dahlbäck
  • Peter Stenvinkel
  • Richard W. James
  • Miguel A. Frias
Organisations
External organisations
  • Karolinska University Hospital
  • Skåne University Hospital
  • University of Geneva
  • Karolinska Institutet
  • University Centre of Legal Medicine
  • Geneva University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
  • Urology and Nephrology

Keywords

  • Cardiomyocyte, End-stage renal disease, High-density lipoprotein, Oxidative stress, Sphingosine-1-phosphate
Original languageEnglish
Article numbere12866
JournalEuropean Journal of Clinical Investigation
Volume48
Issue number2
Early online date2017 Dec 14
Publication statusPublished - 2018 Feb
Publication categoryResearch
Peer-reviewedYes