Plasma Lipid Transfer Protein as a Determinant of the Atherogenicity of Monkey Plasma Lipoproteins

This study was undertaken to determine potential tissue sources of plasma cholesteryl ester transfer protein (CETP), and to assess the influence of CETP on lipoprotein concentra-tions and atherosclerosis. In a group of 28 cynomolgus mon-keys fed high fat, high cholesterol diets, plasma CETP concen-tration was strongly correlated with the abundance of CETP mRNA in liver and in adipose tissue, and with the output of CETP in liver perfusates. Plasma CETP concentration showed a strong inverse correlation with HDL cholesterol concentra-tions (r =-0.62, P < 0.001) and a positive correlation with LDL cholesterol concentration (r = 0.54, P < 0.005) and molec-ular weight (r = 0.57, P < 0.001). The extent ofcoronary artery atherosclerosis was positively correlated with LDL cholesterol concentration and molecular weight, and with plasma CETP concentration. Thus, in monkeys fed an atherogenic diet, indi-vidual variation in CETP mRNA abundance in liver and adi-pose tissue probably plays a major role in the determination of plasma CETP levels. In plasma, CETP influences the distribu-tion of cholesteryl esters between LDL and HDL, and CETP concentration appears to be a key determinant of the relative atherogenicity of the plasma lipoproteins. (J. Clin. Invest. 1991. 87:1559-1566.) Key words: lipid transfer protein, low density lipoprotein * high density lipoprotein * atherosclerosis. dietary fa