HDL proteome in hemodialysis patients: a quantitative nanoflow liquid chromatography-tandem mass spectrometry approach

• Published in: PloS one 2012-03, Vol.7 (3), p.e34107-e34107
• Main Authors: Mangé, Alain, Goux, Aurélie, Badiou, Stéphanie, Patrier, Laure, Canaud, Bernard, Maudelonde, Thierry, Cristol, Jean-Paul, Solassol, Jérôme
• Format: Article
• Language: English
• Subjects: Abnormalities; Aged; Anti-inflammatory agents; Antioxidants; Apolipoprotein C-II - metabolism; Apolipoprotein C-III; Apolipoprotein C-III - metabolism; Apolipoproteins; Biochemistry; Biology; Biomarkers; Blood & organ donations; Cancer; Cardiovascular diseases; Cellular biology; Cholesterol; Cholesterol, HDL - metabolism; Chromatography; Chromatography, High Pressure Liquid; Chronic kidney failure; Comparative analysis; Complement activation; Dialysis; End-stage renal disease; Enzymes; Female; Haptoglobins - metabolism; Health risks; Hemodialysis; High density lipoprotein; Homeostasis; Humans; Inflammation; Inflammatory response; Kidney diseases; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Kidney transplantation; Lipid metabolism; Lipids; Liquid chromatography; Low density lipoprotein; Male; Mass spectrometry; Mass spectroscopy; Medicine; Metabolism; Middle Aged; Nanotechnology; Nephrology; Oxidation; Oxidative stress; Patients; Physiological aspects; Plasma; Pneumonia; Population; Proteins; Proteome - analysis; Proteomics; Renal Dialysis; Scientific imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy; Transferrin - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034107

Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels, qualitative abnormalities of HDL can contribute to an increase in cardiovascular (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse cholesterol transport and the antioxidant and anti-inflammatory properties of HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling and nanoflow liquid chromatography mass spectrometry analysis, was used to generate detailed data on HDL-associated proteins. The HDL composition was compared between seven chronic HD patients and a pool of seven healthy controls. To confirm the proteomics results, specific biochemical assays were then performed in triplicate in the 14 samples as well as 46 sex-matched independent chronic HD patients and healthy volunteers. Of the 122 proteins identified in the HDL fraction, 40 were differentially expressed between the healthy volunteers and the HD patients. These proteins are involved in many HDL functions, including lipid metabolism, the acute inflammatory response, complement activation, the regulation of lipoprotein oxidation, and metal cation homeostasis. Among the identified proteins, apolipoprotein C-II and apolipoprotein C-III were significantly increased in the HDL fraction of HD patients whereas serotransferrin was decreased. In this study, we identified new markers of potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic analysis of the HDL fraction provides an efficient method to identify new and uncharacterized candidate biomarkers of CV risk in HD patients.