Impact of Phospholipid Transfer Protein on Nascent High-Density Lipoprotein Formation and Remodeling
Objective—Phospholipid transfer protein (PLTP), which binds phospholipids and facilitates their transfer between lipoproteins in plasma, plays a key role in lipoprotein remodeling, but its influence on nascent high-density lipoprotein (HDL) formation is not known. The effect of PLTP overexpression on apolipoprotein A-I (apoA-I) lipidation by primary mouse hepatocytes was investigated.
Approach and Results—Overexpression of PLTP through an adenoviral vector markedly affected the amount and size of lipidated apoA-I species that were produced in hepatocytes in a dose-dependent manner, ultimately generating particles that were <7.1 nm but larger than lipid-free apoA-I. These <7.1-nm small particles generated in the presence of overexpressed PLTP were incorporated into mature HDL particles more rapidly than apoA-I both in vivo and in vitro and were less rapidly cleared from mouse plasma than lipid-free apoA-I. The <7.1-nm particles promoted both cellular cholesterol and phospholipid efflux in an ATP-binding cassette transporter A1–dependent manner, similar to apoA-I in the presence of PLTP. Lipid-free apoA-I had a greater efflux capacity in the presence of PLTP than in the absence of PLTP, suggesting that PLTP may promote ATP-binding cassette transporter A1–mediated cholesterol and phospholipid efflux. These results indicate that PLTP alters nascent HDL formation by modulating the lipidated species and by promoting the initial process of apoA-I lipidation.
Conclusions—Our findings suggest that PLTP exerts significant effects on apoA-I lipidation and nascent HDL biogenesis in hepatocytes by promoting ATP-binding cassette transporter A1–mediated lipid efflux and the remodeling of nascent HDL particles.
- Received February 25, 2014.
- Accepted July 8, 2014.
- © 2014 American Heart Association, Inc.