Opposite Effects of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein on the Size Distribution of Plasma High Density Lipoproteins

• Published in: The Journal of biological chemistry 1996-08, Vol.271 (32), p.19058-19065
• Main Authors: Lagrost, Laurent, Athias, Anne, Herbeth, Bernard, Guyard-Dangremont, Valérie, Artur, Yves, Paille, Fran¸ois, Gambert, Philippe, Lallemant, Christian
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.32.19058

The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL 3 , CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37°C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e. , HDL 2b (9.71-12.90 nm), HDL 2a (8.77-9.71 nm), HDL 3a (8.17-8.77 nm), HDL 3b (7.76-8.17 nm), and HDL 3c (7.21-7.76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL 2b (8.66 ± 2.34% versus 7.87 ± 1.83% in controls; p < 0.01) and a significant decrease in the relative abundance of HDL 3a (32.76 ± 3.42% versus 37.87 ± 2.62% in controls; p < 0.05). In contrast, CETP significantly reduced the relative proportion of HDL 2a (33.03 ± 2.53% versus 37.56 ± 6.43% in controls; p < 0.01) but significantly increased the relative proportion of both HDL 3b (21.36 ± 6.97% versus 15.58 ± 7.75% in controls; p < 0.01) and HDL 3c (3.21 ± 4.84% versus 1.13 ± 0.56% in controls; p < 0.05). Finally, in order to assess further the physiological relevance of in vitro observations, CETP activity, PLTP activity, and HDL size distribution were determined in plasmas from 33 alcoholic patients entering a cessation program. Alcohol withdrawal was associated with (i) a significant increase in plasma CETP activity (173.5 ± 70.5%/h/ml before versus 223.2 ± 69.3%/h/ml after alcohol withdrawal, p = 0.0007), (ii) a significant reduction in plasma PLTP activity (473.9 ± 203.7%/h/ml before versus 312.7 ± 148.4%/h/ml after alcohol withdrawal, p = 0.0001), and (iii) a significant shift of large HDL 2b and HDL 2a toward small HDL 3b and HDL 3c . On the one hand, changes in plasma CETP activity correlated negatively with changes in the proportion of HDL 2a ( r = −0.597, p = 0.0002) and positively with changes in the proportion of HDL 3b ( r = 0.457, p = 0.0075). On the other hand, changes in plasma PLTP activity correlated positively with changes in the proportion of HDL 2b ( r = 0.482, p = 0.0045) and negatively with