A Cluster of Proteins Implicated in Kidney Disease Is Increased in High-Density
Lipoprotein Isolated from Hemodialysis Subjects
#MMPMID26011469
Shao B
; de Boer I
; Tang C
; Mayer PS
; Zelnick L
; Afkarian M
; Heinecke JW
; Himmelfarb J
J Proteome Res
2015[Jul]; 14
(7
): 2792-806
PMID26011469
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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.
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