title: A Cluster of Proteins Implicated in Kidney Disease Is Increased in High-Density Lipoprotein Isolated from Hemodialysis Subjects.
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 HDL's 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 HDL's 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.
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Baohai
authors.initials: B
authors.lastname: Shao
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: de Boer
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Mayer
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Leila
authors.initials: L
authors.lastname: Zelnick
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Maryam
authors.initials: M
authors.lastname: Afkarian
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.affiliation: †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D055316:Cystatin C / Q000737:chemistry; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D006435:Renal Dialysis
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D008075:Lipoproteins, HDL
keywords: cardiovascular diseases; end-stage renal disease; hemodialysis; high-density lipoprotein; mass spectrometry; proteomics; selected reaction monitoring; shotgun proteomics