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Journal of Lipid Research, Vol. 43, 1236-1243, August 2002
Copyright © 2002 by Lipid Research, Inc.

Distribution of human plasma PLTP mass and activity in hypo- and hyperalphalipoproteinemia

Tomoichiro Oka^*, Shizuya Yamashita, Takeshi Kujiraoka^*, Mayumi Ito^*, Makoto Nagano^*, Yukiko Sagehashi^*, Tohru Egashira^*, M. Nazeem Nanjee, Ken-ichi Hirano, Norman E. Miller, Yuji Matsuzawa and Hiroaki Hattori^1,*

^* Research Division, R & D Center, BioMedical Laboratory, Inc., 1361-1 Matoba, Kawagoe, Saitama, Japan
Department of Internal Medicine and Molecular Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan
Department of Cardiovascular Biochemistry, St. Bartholomew's and the Royal London, School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, United Kingdom

¹ To whom correspondence should be addressed. e-mail: hhiro{at}bml.co.jp

Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism and reverse cholesterol transport. We have recently reported that plasma PLTP concentration correlates positively with plasma HDL cholesterol (HDL-C) but not with PLTP activity in healthy subjects. We have also shown that PLTP exists as active and inactive forms in healthy human plasma. In the present study, we measured plasma PLTP concentration and PLTP activity, and analyzed the distribution of PLTP in normolipidemic subjects (controls), cholesteryl ester transfer protein (CETP) deficiency, and hypo-alphalipoproteinemia (hypo-ALP). Plasma PLTP concentration was significantly lower (0.7 ± 0.4 mg/l, mean ± SD, n = 9, P < 0.001) in the hypo-ALP subjects, and significantly higher (19.5 ± 4.3 mg/l, n = 17, P < 0.001) in CETP deficiency than in the controls (12.4 ± 2.3 mg/l, n = 63). In contrast, we observed no significant differences in plasma PLTP activity between controls, hypo-ALP subjects, and CETP deficiency (6.2 ± 1.3, 6.1 ± 1.8, and 6.8 ± 1.2 µmol/ml/h, respectively). There was a positive correlation between PLTP concentration and plasma HDL-C (r = 0.81, n = 89, P < 0.001). By size exclusion chromatography analysis, we found that the larger PLTP containing particles without PLTP activity (inactive form of PLTP) were almost absent in the plasma of hypo-ALP subjects, and accumulated in the plasma of CETP deficiency compared with those of controls.

These results indicate that the differences in plasma PLTP concentrations between hypo-ALP subjects, CETP deficiency, and controls are mainly due to the differences in the amount of the inactive form of PLTP.

Abbreviations: ABCA1, ATP-binding cassette transporter A1; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FC, free cholesterol; HRP, horseradish peroxidase; hyper-ALP, hyperalphalipoproteinemia; hypo-ALP, hypoalphalipoproteinemia; PLTP, phospholipid transfer protein

Supplementary key words phospholipid transfer protein • lecithin:cholesterol acyltransferase deficiency • Tangier disease • apolipoprotein A-I deficiency • familial high density lipoprotein deficiency • cholesteryl ester transfer protein deficiency

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