The effect of phospholipid transfer protein on lipoprotein metabolism and atherosclerosis.

Phospholipid transfer protein (PLTP) is a member of the lipid transfer/lipopolysaccharide binding protein gene family. Recently, the crystal structure of one of the members of the gene family, bactericidal permeability increasing protein, was solved, providing potential insights into the mechanisms of action of PLTP. These molecules contain intrinsic lipid binding sites and appear to act as carrier proteins that shuttle between lipoproteins to redistribute lipids. The phenotype of PLTP transgenic and gene knock out mice indicates that PLTP plays a major role in the metabolism of high-density lipoprotein (HDL) and apoB-containing lipoproteins and thereby influences the concentration, apolipoprotein content, and size of lipoprotein particles in plasma. Recent data indicate that PLTP deficiency in mice is associated with a decrease of atherosclerosis, despite decreased HDL levels. At lease two underlined mechanisms are involved in the reduction of atherosclerosis in PLTP deficient status, 1) reduction of apoB-containing lipoprotein production and levels; and 2) increase of anti-oxidation potential. Human studies indicated that PLTP activity positively correlated with aging, obesity, diabetes and coronary artery disease. A challenge for the future will be the inhibition of PLTP for therapeutic benefit.