A Cluster of Proteins Implicated in Kidney Disease Is Increased in High-Density Lipoprotein Isolated from Hemodialysis Subjects

Baohai Shao, Ian De Boer, Chongren Tang, Philip S. Mayer, Leila Zelnick, Maryam Afkarian, Jay W. Heinecke, Jonathan Himmelfarb

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Cardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) patients treated with hemodialysis. An important contributor might be a decline in the cardioprotective effects of high-density lipoprotein (HDL). One important factor affecting HDLs cardioprotective properties may involve the alterations of protein composition in HDL. In the current study, we used complementary proteomics approaches to detect and quantify relative levels of proteins in HDL isolated from control and ESRD subjects. Shotgun proteomics analysis of HDL isolated from 20 control and 40 ESRD subjects identified 63 proteins in HDL. Targeted quantitative proteomics by isotope-dilution selective reaction monitoring revealed that 22 proteins were significantly enriched and 6 proteins were significantly decreased in ESRD patients. Strikingly, six proteins implicated in renal disease, including B2M, CST3, and PTGDS, were markedly increased in HDL of uremic subjects. Moreover, several of these proteins (SAA1, apoC-III, PON1, etc.) have been associated with atherosclerosis. Our observations indicate that the HDL proteome is extensively remodeled in uremic subjects. Alterations of the protein cargo of HDL might impact HDLs proposed cardioprotective properties. Quantifying proteins in HDL may be useful in the assessment of cardiovascular risk in patients with ESRD and in assessing response to therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)2792-2806
Number of pages15
JournalJournal of Proteome Research
Volume14
Issue number7
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • cardiovascular diseases
  • end-stage renal disease
  • hemodialysis
  • high-density lipoprotein
  • mass spectrometry
  • proteomics
  • selected reaction monitoring
  • shotgun proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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