title: HIV inhibits endothelial reverse cholesterol transport through impacting subcellular Caveolin-1 trafficking.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection leads to decreased reverse cholesterol transport (RCT) in macrophages, and Nef mediated down-regulation and redistribution of ATP-binding cassette transporter A1 (ABCA1) are identified as key factors for this effect. This may partially explain the increased risk of atherosclerosis in HIV infected individuals. Since endothelial dysfunction is key in the initial stages of atherosclerosis, we sought to determine whether RCT was affected in human aortic endothelial cells (HAECs).
  
  
  RESULTS
  We found that apoA-I does not significantly stimulate cholesterol efflux in HAECs while cholesterol efflux to high-density lipoprotein (HDL) was dramatically reduced in HAECs co-cultured with HIV infected cells. Studies with wild type and Nef defective HIV revealed no significant differences suggesting that multiple factors are working perhaps in concert with Nef to affect cholesterol efflux to HDL from HAECs. Interestingly, treating HAECs with recombinant Nef showed similar effect in HDL mediated cholesterol efflux as observed in HAECs co-cultured with HIV infected cells. Using a detergent-free based subcellular fractionation approach, we demonstrated that exposure of HAECs to HIV infected cells or Nef alone disrupts caveolin 1 (Cav-1) subcellular trafficking upon HDL stimulation. Moreover, Nef significantly enhanced tyrosine 14 phosphorylation of Cav-1 which may have an impact on recycling of Cav-1 and caveolae.
  
  
  CONCLUSIONS
  These results suggest that HIV interferes with cholesterol efflux by HDL in HAECs through the disruption of Cav-1s' cellular distribution and that multiple factors are involved, possibly including Nef, for the inhibition of HDL mediated cholesterol efflux and alteration of cellular distribution of Cav-1.
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, 32611, USA. shanlin@ufl.edu.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, 32611, USA. pnadeau@ufl.edu.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nadeau
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, 32611, USA. mergiaa@ufl.edu.
authors.forename: Ayalew
authors.initials: A
authors.lastname: Mergia
mesh_terms: D001692:Biological Transport; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006678:HIV / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans
chemical_list: D051242:Caveolin 1; D002784:Cholesterol