Abstract 16325: Shotgun Proteomics Analysis of HDL in Patients With Cholesteryl Ester Transfer Protein Deficiency
Background: Plasma HDL-C levels are negatively correlated with the incidence of cardiovascular disease (CVD). However, inhibition or deficiency of cholesteryl ester transfer protein (CETP) could not improve the outcome of CVD events so far, in spite of increased HDL-C levels. HDL particles carry a variety of proteins, some of which are known to have anti-atherogenic functions. We hypothesized that CETP deficiency may alter the protein composition of HDL particles.
Methods: In the current study, we enrolled 8 homozygous CETP-deficient (CETP-D) patients, whose serum CETP mass was less than 0.1 μg/mL, and compared with 8 normolipidemic controls. We performed shotgun proteomic analysis to investigate the proteome of ultracentrifugally isolated HDL. Spectral counting and spectral index were assessed to quantify relative protein abundance between the two groups.
Results: We identified 79 HDL-associated proteins involved in lipid metabolism, protease inhibition, complement regulation, and acute-phase response, including 11 newly identified HDL-associated proteins. CETP was only seen in controls, and spectral counts of apolipoprotein (Apo)E were increased in CETP-D patients compared with those of controls (62.4±8.4 vs 41.8±3.3, p<0.001), which is concordant with our previous report. Complement regulatory proteins such as C3, C4a, C4b, and C9 were detected and also enriched in CETP-D patients. Furthermore, interestingly, ApoC3 and angiopoietin-like 3 (ANGPTL3), both of which have an inhibitory effect on lipoprotein lipase activity, were enriched in CETP-D patients compared with controls (30.9±4.3 vs 26.0±1.9, 2.4±1.2 vs 0.4±1.1, respectively; p<0.01). As shown in the Figure of spectral index, protein composition of HDL in CETP-D patients was quite different from that of controls.
Conclusion: We have characterized HDL-associated proteins in CETP-D patients. These proteomic changes might be responsible for the enhanced atherogenicity of CETP-D patients.
Author Disclosures: T. Okada: None. T. Ohama: None. K. Kanno: None. H. Matsuda: None. M. Sairyo: None. Y. Zhu: None. A. Saga: None. T. Kobayashi: None. D. Masuda: Research Grant; Significant; Merck Sharp & Dohme Corp.. M. Koseki: None. M. Nishida: None. Y. Sakata: None. S. Yamashita: Research Grant; Modest; Kyowa Medex Co., Ltd.. Research Grant; Significant; Merck Sharp & Dohme Corp..
- © 2016 by American Heart Association, Inc.