title: Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease.
abstract: This study compared the molecular lipidomic profile 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 identified 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profile in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N-acyltaurines were significantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were significantly 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 identified individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These findings 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 profile of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease.
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Reis
authors.affiliation: Centro de Estudios do Ambiente e do Mar (CESAM), Department of Chemistry, Universidade de Aveiro, Portugal.
authors.forename: Alisa
authors.initials: A
authors.lastname: Rudnitskaya
authors.affiliation: Clinical Pharmacology Unit, British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Pajaree
authors.initials: P
authors.lastname: Chariyavilaskul
authors.affiliation: Clinical Pharmacology Unit, British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhaun
authors.affiliation: Clinical Pharmacology Unit, British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Melville
authors.affiliation: Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Goddard
authors.affiliation: Clinical Pharmacology Unit, British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pitt
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spickett
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000097:blood; D010743:Phospholipids / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D002788:Cholesterol Esters; D008055:Lipids; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; C007045:cholesteryl sulfate
keywords: N-acyltaurine; cholesterol; cholesterol sulfate; dyslipidemias; inflammation; mass spectrometry; partial least squares discriminant analysis; phospholipids