Increased risk of atherosclerosis by elevated plasma levels of phospholipid transfer protein.
Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (</=1.5-fold). The mice were given a high fat, high cholesterol diet, which resulted in hypercholesterolemia in all animals. HDL concentrations were dramatically reduced in PLTP-overexpressing animals when compared with LDL receptor controls, whereas VLDL + LDL cholesterol levels were identical. Susceptibility to atherosclerosis was increased in a PLTP dose-responsive manner. We conclude that PLTP increases susceptibility to atherosclerosis by lowering HDL concentrations, and therefore we suggest that an increase in PLTP is a novel, long term risk factor for atherosclerosis in humans.
van Haperen
Rien
R
Department of Cell Biology & Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
van Tol
Arie
A
van Gent
Teus
T
Scheek
Leo
L
Visser
Pim
P
van der Kamp
Arthur
A
Grosveld
Frank
F
de Crom
Rini
R
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism; D004032:Diet; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins; D012307:Risk Factors
D002352:Carrier Proteins; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins