Phospholipid Transfer Protein and Atherosclerosis

Genetic studies in humans and mice show that two related plasma lipid transfer proteins (cholesteryl ester transfer protein [CETP] and phospholipid transfer protein [PLTP]) have distinct roles in lipoprotein metabolism, despite their homology.1 In human homozygous CETP deficiency, HDL levels are massively elevated, and LDL levels are moderately decreased.2 While a human PLTP deficiency state has not been described, PLTP-/- mice have ≈50% reductions in HDL levels, indicating the essential role of PLTP in transferring phospholipids from triglyceride-carrying lipoproteins into HDL.3 When crossed with apoE-/- mice, or apoB transgenic mice, PLTP deficiency results in reductions in apoB lipoproteins, revealing a role of intracellular PLTP in the hepatic secretion of apoB lipoproteins.4 See page 1601 Crosses of PLTP deficient mice into apoB transgenic, apoE-/-, or LDL R-/- backgrounds resulted in diminished atherosclerosis in all three of these standard mouse atherosclerosis models.4 In part this was related to the reduction of levels of apoB containing lipoproteins seen in apoB transgenic and apoE-/- mice. However, an anti-atherogenic effect of …