title: Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo.
abstract: OBJECTIVE
  Apolipoprotein F (ApoF) is a protein component of several lipoprotein classes including HDL. It is also known as lipid transfer inhibitor protein (LTIP) based on its ability to inhibit lipid transfer between lipoproteins ex vivo. We sought to investigate the role of ApoF in HDL metabolism.
  
  
  RESULTS
  Adeno-associated viruses (AAV) based on serotype 8, were used to overexpress either murine or human ApoF in mice. Overexpression of murine ApoF significantly reduced total cholesterol levels by 28% (P<0.001), HDL by 27% (P<0.001), and phospholipid levels by 19% (P<0.001). Overexpression of human ApoF had similar effects. Human ApoF was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the ApoF in human plasma was found on HDL(3), with only a small amount on LDL. Overexpression of mouse ApoF accelerated the plasma clearance of [(3)H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing ApoF showed improved macrophage cholesterol efflux on a per HDL-C basis.
  
  
  CONCLUSIONS
  ApoF overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. ApoF may be an important determinant of HDL metabolism and reverse cholesterol transport.
authors.affiliation: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lagor
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brown
authors.forename: Sue-Anne
authors.initials: SA
authors.lastname: Toh
authors.forename: John S
authors.initials: JS
authors.lastname: Millar
authors.forename: Ilia V
authors.initials: IV
authors.lastname: Fuki
authors.forename: Margarita
authors.initials: M
authors.lastname: de la Llera-Moya
authors.forename: Tiffany
authors.initials: T
authors.lastname: Yuen
authors.forename: George
authors.initials: G
authors.lastname: Rothblat
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Billheimer
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D001853:Bone Marrow / Q000502:physiology; D002460:Cell Line; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D003001:Cloning, Molecular; D000229:Dependovirus / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000196:embryology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000097:blood; D010957:Plasmids; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D008076:Cholesterol, HDL; D010743:Phospholipids; D014280:Triglycerides; C036321:apolipoprotein F; D002784:Cholesterol; D000410:Alanine Transaminase