HDL Proteome in Hemodialysis Patients: A Quantitative Nanoflow Liquid Chromatography-Tandem Mass Spectrometry Approach

Abstract

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.

HDL and cholesterol: life after the divorce?

“…When associated with HDL, Hb also likely acts as an antioxidant and may mediate HDL transport of iron. Hb is not the only iron-binding protein on HDL, as serotransferrin is also highly abundant on HDL and was recently found to be decreased on HDL after hemodialysis in patients with end-stage renal disease ( 79 ). HDL likely participates in the transport of iron from the gut and phagocytic cells to targeted recipient cells through serotransferrin and thus contributes to global homeostasis and cellular metabolism and physiology.…”

Effect of an Isoenergetic Traditional Mediterranean Diet on the High-Density Lipoprotein Proteome in Men with the Metabolic Syndrome

“…The number of proteins identified was somewhat smaller than what has previously been achieved using iTRAQ labeling [17]. However, all proteins reliably identified and quantified by iTRAQ in our study have been shown to belong to the HDL proteome, and they represent the most abundant proteins found in this fraction [17,18,19,20,21,22]. …”

Epidemiology: Disease Associations and Modulators of HDL-Related Biomarkers

“…Recent reports have shown that HDL-C may be a biomarker for diseases like psoriasis (Holzer et al 2012), rheumatoid arthritis (Raterman et al 2013), and liver fibrosis in hepatitis C patients (Gangadharan et al 2012). Alterations in HDL composition have been observed also in hemodialysis patients (Mangé et al 2012). Special interest has been recently focused on HDL in cancer patients.…”