Dynamic changes in mouse lipoproteins induced by transiently expressed human phospholipid transfer protein (PLTP): importance of PLTP in pre beta-HDLgeneration

The plasma phospholipid transfer protein (PLTP) plays an important role in the regulation of plasma high density lipoprotein (HDL) levels and governs the distribution of HDL sub-populations. In the present study, adenovirus m ediated overexpression of human PLTP in mice was employed to investigate th e distribution of PLTP in serum and its effect on plasma lipoproteins. Gel filtration experiments showed that the distributions of PLTP activity and m ass in serum are different, suggesting that human PLTP circulated in mouse plasma as two distinct forms, one with high and the other with low specific activity. Our study further demonstrates that overexpression of PLTP leads to depletion of HDL and that, as PLTP activity declines, replenishment of the HDL fraction occurs. During this process, the lipoprotein profile displ ays transient particle populations, including apoA-IV and apoE-rich particl es in the LDL size range and small particles containing apoA-II only. The p ossible role of these particles in HDL reassembly is discussed. The increas ed PLTP activity enhanced the ability of mouse sera to produce prep-HDL. Th e present results provide novel evidence that PLTP is an important regulato r of HDL metabolism and plays a central role in the reverse cholesterol tra nsport (RCT) process. (C) 2001 Elsevier Science Inc. All rights reserved.