出版社:American Society for Biochemistry and Molecular Biology
摘要:Plasma cholesteryl ester transfer protein (CETP) has a profoundeffect on neutral lipid transfers between HDLs and apolipoproteinB (apoB)-containing lipoproteins when it is expressed in combinationwith human apoA-I in HuAI/CETP transgenic (Tg) rodents. In thepresent study, human apoA-I-mediated lipoprotein changes inHuAI/CETPTg rats are characterized by 3- to 5-fold incrementsin the apoB-containing lipoprotein-to-HDL cholesterol ratio,and in the cholesteryl ester-to-triglyceride ratio in apoB-containinglipoproteins. These changes occur despite no change in plasmaCETP concentration in HuAI/CETPTg rats, as compared with CETPTgrats. A number of HDL apolipoproteins, including rat apoA-Iand rat apoC-I are removed from the HDL surface as a resultof human apoA-I overexpression. Rat apoC-I, which is known toconstitute a potent inhibitor of CETP, accounts for approximatelytwo-thirds of CETP inhibitory activity in HDL from wild-typerats, and the remainder is carried by other HDL-bound apolipoproteininhibitors. It is concluded that human apoA-I overexpressionmodifies HDL particles in a way that suppresses their abilityto inhibit CETP. An apoC-I decrease in HDL of HuAI/CETPTg ratscontributes chiefly to the loss of the CETP-inhibitory potentialthat is normally associated with wild-type HDL.Supplementary key words apolipoprotein A-I • cholesteryl ester transfer protein • apolipoprotein C-I
Abbreviations: apoA-I, apolipoprotein A-I; CETP, cholesteryl ester transfer protein; LCAT, lecithin:cholesterol acyltransferase; PLTP, phospholipid transfer protein