Particle number analysis of lipoprotein subclasses by gel permeation HPLC in patients with cholesteryl ester transfer protein deficiency

• Published in: PloS one Vol. 13; no. 1; p. e0190875
• Main Authors: Okada, Takeshi, Ohama, Tohru, Okazaki, Mitsuyo, Kanno, Kotaro, Matsuda, Hibiki, Sairyo, Masami, Zhu, Yinghong, Saga, Ayami, Kobayashi, Takuya, Masuda, Daisaku, Koseki, Masahiro, Nishida, Makoto, Sakata, Yasushi, Yamashita, Shizuya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.01.2018; Public Library of Science (PLoS)
• Subjects: Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Cardiology; Cardiovascular diseases; Cholesterol; Cholesteryl ester transfer protein; Chromatography; Counseling services; High density lipoprotein; High density lipoproteins; High performance liquid chromatography; Lipids; Lipoproteins; Lipoproteins (very low density); Liquid chromatography; Low density lipoprotein; Medicine; Medicine and Health Sciences; Particle size; Penetration; Physical Sciences; Physiological aspects; Protein deficiency; Proteins; Quarks; Transport proteins; Triglycerides; University graduates; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0190875

We previously reported that patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) have a higher prevalence of atherosclerotic cardiovascular disease, in spite of increased HDL-C levels. However, characterization of HDL in CETP-D has not been well described. Therefore, we examined HDL particle number (PN) rather than HDL-C level. Nine patients with CETP-D and 9 normolipidemic subjects were enrolled. We performed gel permeation high-performance liquid chromatography (GP-HPLC) analysis, determined the cholesterol and triglyceride composition of all lipoprotein subclasses, and calculated the PN of each subclass, which consisted of 3 VLDL (large, medium, and small), 4 LDL (large, medium, small, and very small), and 5 HDL (very large, large, medium, small, and very small) subclasses. The PNs of large and medium LDL were significantly lower in CETP-D than that in healthy subjects (0.66- and 0.63-fold decrease, respectively; p<0.001), whereas the PN of very small LDL, which is known to be atherogenic, was significantly higher (1.36-fold increase, p = 0.016). The PNs of very large and large HDL in CETP-D were markedly higher than that in healthy subjects (19.9- and 4.5-fold increase, respectively; p<0.001), whereas the PNs of small and very small HDL, which have more potent anti-atherogenic functions, were significantly lower (0.76- and 0.61-fold decrease, respectively; p<0.001). We have assessed the PNs of detailed subclasses of patients with CETP-D for the first time. The PN of larger HDL was markedly increased, that of smaller HDL was decreased, and that of very small LDL was increased, suggesting that CETP-D has pro-atherogenic lipoprotein properties.