Takeshi Okada1, Tohru Ohama2, Kazuaki Takafuji3, Kotaro Kanno1, Hibiki Matsuda1, Masami Sairyo1, Yinghong Zhu1, Ayami Saga1, Takuya Kobayashi1, Daisaku Masuda1, Masahiro Koseki1, Makoto Nishida4, Yasushi Sakata1, Shizuya Yamashita5. 1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 2. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Osaka, Japan. 3. Department of Bio-System Pharmacology, Osaka University Graduate School Graduate, School of Medicine, Osaka, Japan. 4. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Health Care Division, Health and Counseling Center, Osaka University, Osaka, Japan. 5. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Community Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Cardiology, Rinku General Medical Center, Osaka, Japan. Electronic address: shizu@imed2.med.osaka-u.ac.jp.
Abstract
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.
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.
Authors: W Sean Davidson; Amy S Shah; Hannah Sexmith; Scott M Gordon Journal: Biochim Biophys Acta Mol Cell Biol Lipids Date: 2021-11-18 Impact factor: 4.698
Authors: Deanna L Plubell; Alex M Fenton; Sara Rosario; Paige Bergstrom; Phillip A Wilmarth; Wayne M Clark; Neil A Zakai; Joseph F Quinn; Jessica Minnier; Nabil J Alkayed; Sergio Fazio; Nathalie Pamir Journal: Circ Res Date: 2020-08-26 Impact factor: 17.367