title: Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice.
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 degrees C reveals a 2- to 3-fold increase in the formation of pre-beta-HDL compared with plasma from wild-type mice. Although pre-beta-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-beta-HDL.
authors.affiliation: MGC-Department of Cell Biology and Genetics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Haperen
authors.forename: A
authors.initials: A
authors.lastname: van Tol
authors.forename: P
authors.initials: P
authors.lastname: Vermeulen
authors.forename: M
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: T
authors.initials: T
authors.lastname: van Gent
authors.forename: P
authors.initials: P
authors.lastname: van den Berg
authors.forename: S
authors.initials: S
authors.lastname: Ehnholm
authors.forename: F
authors.initials: F
authors.lastname: Grosveld
authors.forename: A
authors.initials: A
authors.lastname: van der Kamp
authors.forename: R
authors.initials: R
authors.lastname: de Crom
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000032:analysis; D001161:Arteriosclerosis / Q000517:prevention & control*; D001769:Blood; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D002850:Chromatography, Gel; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins
chemical_list: D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol