Abstract 167: PLTP Acts in Concert with SAA to Reduce Plasma HDL Levels in Mice and Modulates Nascent HDL Formation in Hepatocytes
Phospholipid transfer protein (PLTP), which binds phospholipids and facilitates their transfer between lipoproteins in plasma, plays a key role in lipoprotein remodeling. PLTP levels increase during acute inflammation and increased PLTP activity is associated with the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) as seen in patients with type 2 diabetes and cardiovascular disease. SAA, an HDL apolipoprotein, is highly induced during inflammation. In this study we investigated whether HDL remodeling by PLTP is affected by SAA, and the significance of PLTP on HDL biogenesis. Over-expression of PLTP in mice using an adenoviral vector reduced HDL-C and phospholipid (PL) in a dose dependent manner with the liberation of lipid-poor apoA-I. Co-expression of PLTP and SAA produced a significantly greater reduction in HDL-C and PL than expression of either PLTP or SAA alone. Studies were carried out to examine the lipidation of apoA-I and formation of nascent HDL particles by primary mouse hepatocytes. Over-expression of PLTP in hepatocytes markedly affected the levels as well as the species of nascent HDL particles produced by cells. Although the formation of smaller nascent HDLs was reduced by PLTP, the formation of the larger HDLs was increased. PLTP expression in hepatocytes did not change ABCA1 levels. Co-expression of SAA with PLTP exerted only a modest effect on the levels and types of HDL generated in the presence of PLTP. Our findings suggest that the remodeling of plasma HDL by PLTP and SAA contributes to the reduced HDL-C levels observed during inflammation. PLTP also significantly affects apoA-I lipidation and nascent HDL biogenesis in hepatocytes.
- © 2012 by American Heart Association, Inc.