Increased Risk of Atherosclerosis by Elevated Plasma Levels of Phospholipid Transfer Protein

• Published in: The Journal of biological chemistry 2002-12, Vol.277 (50), p.48938-48943
• Main Authors: van Haperen, Rien, van Tol, Arie, van Gent, Teus, Scheek, Leo, Visser, Pim, van der Kamp, Arthur, Grosveld, Frank, de Crom, Rini
• Format: Article
• Language: English
• Subjects: Animals; Arteriosclerosis - blood; Carrier Proteins - blood; Cholesterol, HDL - blood; Cholesterol, VLDL - blood; Cholesterol, VLDL - metabolism; Diet; Male; Membrane Proteins - blood; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phospholipid Transfer Proteins; Risk Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M209128200

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.