title: Impact of phospholipid transfer protein on nascent high-density lipoprotein formation and remodeling.
abstract: 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.
  
  
  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.
authors: From the Department of Internal Medicine (A.J., J.M.W., D.R.v.d.W.), Department of Pharmacology and Nutritional Sciences (A.J., J.M.W., N.R.W., D.R.v.d.W.), Department of Molecular and Cellular Biochemistry (D.R.v.d.W.), and Saha Cardiovascular Research Center (A.J., J.M.W., N.R.W., D.R.v.d.W.), University of Kentucky, Lexington; and Department of Veterans Affairs Medical Center (N.R.W., D.R.v.d.W.), Lexington, KY.
authors: Ailing
authors: A
authors: Ji
authors: From the Department of Internal Medicine (A.J., J.M.W., D.R.v.d.W.), Department of Pharmacology and Nutritional Sciences (A.J., J.M.W., N.R.W., D.R.v.d.W.), Department of Molecular and Cellular Biochemistry (D.R.v.d.W.), and Saha Cardiovascular Research Center (A.J., J.M.W., N.R.W., D.R.v.d.W.), University of Kentucky, Lexington; and Department of Veterans Affairs Medical Center (N.R.W., D.R.v.d.W.), Lexington, KY.
authors: Joanne M
authors: JM
authors: Wroblewski
authors: From the Department of Internal Medicine (A.J., J.M.W., D.R.v.d.W.), Department of Pharmacology and Nutritional Sciences (A.J., J.M.W., N.R.W., D.R.v.d.W.), Department of Molecular and Cellular Biochemistry (D.R.v.d.W.), and Saha Cardiovascular Research Center (A.J., J.M.W., N.R.W., D.R.v.d.W.), University of Kentucky, Lexington; and Department of Veterans Affairs Medical Center (N.R.W., D.R.v.d.W.), Lexington, KY.
authors: Nancy R
authors: NR
authors: Webb
authors: From the Department of Internal Medicine (A.J., J.M.W., D.R.v.d.W.), Department of Pharmacology and Nutritional Sciences (A.J., J.M.W., N.R.W., D.R.v.d.W.), Department of Molecular and Cellular Biochemistry (D.R.v.d.W.), and Saha Cardiovascular Research Center (A.J., J.M.W., N.R.W., D.R.v.d.W.), University of Kentucky, Lexington; and Department of Veterans Affairs Medical Center (N.R.W., D.R.v.d.W.), Lexington, KY. dvwest1@uky.edu.
authors: Deneys R
authors: DR
authors: van der Westhuyzen
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D022781:Hepatocytes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002784:Cholesterol; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; C577833:Abca1 protein, mouse; C510091:phospholipid transfer protein, mouse
keywords: cholesterol; hepatocytes; nascent HDL; phospholipid transfer protein