Highlights
- •We have characterized the proteome of HDL in healthy subjects and patients with CETP-D.
- •We identified 79 HDL-associated proteins, 5 of which were newly identified.
- •ApoE, apoC-III, and complement C3 and C4b were significantly increased in HDL of CETP-D.
- •We identified ANGPTL3 as an HDL-associated protein, which was increased in CETP-D.
- •These proteomic changes might be partly responsible for atherogenicity of CETP-D.
Background
We previously reported that the patients with cholesteryl ester transfer protein (CETP)
deficiency (CETP-D) show marked changes in the size and lipid compositions of high-density
lipoprotein (HDL) and that they are not protected from atherosclerotic cardiovascular
diseases, despite increased serum HDL-cholesterol (HDL-C) levels. HDL particles carry
a variety of proteins, some of which are known to have antiatherogenic functions.
Objective
This study aimed to investigate the protein composition of HDL particles in patients
with CETP-D.
Methods
Eight patients with complete deficiency of CETP and 8 normolipidemic healthy subjects
were enrolled. We performed shotgun proteomic analysis to investigate the proteome
of ultracentrifugally isolated HDL.
Results
We identified 79 HDL-associated proteins involved in lipid metabolism, protease inhibition,
complement regulation, and acute-phase response, including 5 potential newly identified
HDL-associated proteins such as angiopoietin-like3 (ANGPTL3). Spectral counts of apolipoprotein
(apo) E were increased in patients with CETP-D compared with controls (60.3 ± 6.9
vs 43.7 ± 2.5, P < .001), which is concordant with our previous report. Complement regulatory proteins
such as C3, C4a, C4b, and C9 were also significantly enriched in HDL from patients
with CETP-D. Furthermore, apoC-III and ANGPTL3, both of which are now known to associate
with increased atherosclerotic cardiovascular diseases, were enriched in patients
with CETP-D compared with normolipidemic subjects (35.9 ± 5.3 vs 27.1 ± 3.7, 2.3 ± 1.1
vs 0.4 ± 1.1, respectively; P < .01).
Conclusion
We have characterized HDL-associated proteins in patients with CETP-D. We identified
a significant increase in the amount of apoE, apoC-III, ANGPTL3, and complement regulatory
proteins. These proteomic changes might be partly responsible for the enhanced atherogenicity
of patients with CETP-D.
Keywords
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Article info
Publication history
Published online: January 10, 2019
Accepted:
January 7,
2019
Received:
July 18,
2018
Identification
Copyright
© 2019 National Lipid Association. All rights reserved.
