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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1482.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Delineation of the Role of Pre-ß₁-HDL in Cholesterol Efflux Using Isolated Pre-ß₁-HDL

Dmitri Sviridov; Osamu Miyazaki; Kally Theodore; Anh Hoang; Isamu Fukamachi; Paul Nestel

From the Baker Medical Research Institute (D.S., K.T., A.H., P.N.), Melbourne, Australia, and Diagnostic Research Laboratories (O.M., I.F.), Daiichi Pure Chemicals Ltd, Tokyo, Japan.

Correspondence to Dr Dmitri Sviridov, Baker Medical Research Institute, PO Box 6492, St. Kilda Rd, Central, Melbourne, Victoria 8008, Australia. E-mail Dmitri.Sviridov{at}Baker.edu.au

Objective— The role of pre-ß₁-high density lipoprotein (pre-ß₁-HDL) in cholesterol efflux was investigated by separating human plasma into purified pre-ß₁-HDL and pre-ß₁-HDL–deficient plasma by using a monoclonal antibody specifically reacting with pre-ß₁-HDL.

Methods and Results— When compared with whole plasma, pre-ß₁-HDL–deficient plasma was equally efficient in promoting cholesterol efflux from human skin fibroblasts and THP-1 human macrophage cells. When added at the same apolipoprotein A-I concentration, pre-ß₁-HDL was less effective than whole plasma in promoting cholesterol efflux from fibroblasts but equally effective in promoting cholesterol efflux from THP-1 cells. However, pre-ß₁-HDL–deficient plasma reconstituted with 16% pre-ß₁-HDL was more active than whole plasma, demonstrating that pre-ß₁-HDL does promote cholesterol efflux actively. The amount of cellular cholesterol present in reisolated pre-ß₁-HDL was 1.5- to 2-fold greater after incubation of the cells with whole plasma than after incubation of the cells with pre-ß₁-HDL–deficient plasma or plasma treated with the anti–pre-ß₁-HDL antibody. However, the anti–pre-ß₁-HDL antibody did not inhibit cholesterol efflux.

Conclusions— We conclude that whereas pre-ß₁-HDL is capable of taking up cellular cholesterol, its presence in plasma is not essential for cholesterol efflux, at least in vitro. Instead, pre-ß₁-HDL may be the first product of apolipoprotein A-I lipidation during the formation of HDL but may not play a major role in transferring cellular cholesterol to HDL.

Key Words: atherosclerosis • reverse cholesterol transport • cholesterol efflux • high density lipoproteins • pre-ß₁-HDL

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