Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

Ana Reis , Alisa Rudnitskaya, Pajaree Chariyavilaskul, Neeraj Dhaun, Vanessa Melville, Jane Goddard, David J. Webb, Andrew R. Pitt, Corinne M. Spickett*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

This study compared the molecular lipidomic profi le of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identifi ed 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profi le in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N -acyltaurines were signifi cantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were signifi cantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identifi ed individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These fi ndings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profi le of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. -Reis, A., A. Rudnitskaya, P. Chariyavilaskul, N. Dhaun, V. Melville, J. Goddard, D. J. Webb, A. R. Pitt, and C. M. Spickett. Topdown lipidomics of low density lipoprotein reveal altered lipid profi les in advanced chronic kidney disease. J. Lipid Res. 2015.

Original languageEnglish
Pages (from-to)413-422
Number of pages10
JournalJournal of Lipid Research
Volume56
Issue number2
Early online date25 Jan 2014
DOIs
Publication statusPublished - 1 Feb 2015

Bibliographical note

This research was originally published in Journal of Lipid Research. Reis, A., Rudnitskaya, A., Chariyavilaskul, P., Dhaun, N., Melville, V., Goddard, J., ... Spickett, C. M.Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease. Journal of Lipid Research. 2015; 56:413-422. © the American Society for Biochemistry and Molecular Biology.

Keywords

  • Cholesterol
  • Cholesterol sulfate
  • Dyslipidemias
  • Inflammation
  • Mass spectrometry
  • N -acyltaurine
  • Partial least squares discriminant analysis
  • Phospholipids

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