Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1082-1088
© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Human Plasma Phospholipid Transfer Protein Increases the Antiatherogenic Potential of High Density Lipoproteins in Transgenic Mice
From MGC–Department of Cell Biology and Genetics (R.v.H., F.G., A.v.d.K., R.d.C.) and the Department of Biochemistry, Cardiovascular Research Institute COEUR (A.v.T., P.V., T.v.G., P.v.d.B.), Erasmus University Rotterdam, Rotterdam, the Netherlands; the Department of Biochemistry, National Public Health Institute (M.J., S.E.), Helsinki, Finland; and the Department of Vascular Surgery, Academic Hospital "Dijkzigt" (R.d.C.), Rotterdam, the Netherlands.
Correspondence to Dr Arie van Tol, Department of Biochemistry, Erasmus University Rotterdam, Dr. Molenwaterplein 50, PO Box 1738, 3000 DR Rotterdam, Netherlands. E-mail VANTOL{at}BC1.FGG.EUR.NL
Abstract—Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress human PLTP were generated. Compared with wild-type mice, these mice show a 2.5- to 4.5-fold increase in PLTP activity in plasma. This results in a 30% to 40% decrease of plasma levels of HDL cholesterol. Incubation of plasma from transgenic animals at 37°C reveals a 2- to 3-fold increase in the formation of pre-ß-HDL compared with plasma from wild-type mice. Although pre-ß-HDL is normally a minor subfraction of HDL, it is known to be a very efficient acceptor of peripheral cell cholesterol and a key mediator in reverse cholesterol transport. Further experiments show that plasma from transgenic animals is much more efficient in preventing the accumulation of intracellular cholesterol in macrophages than plasma from wild-type mice, despite lower total HDL concentrations. It is concluded that PLTP can act as an antiatherogenic factor preventing cellular cholesterol overload by generation of pre-ß-HDL.
Key Words: atherosclerosis • pre-ß-HDL • transgenic mice • macrophages • phospholipid transfer protein
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