title: The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA).
  
  
  METHODS
  We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg).
  
  
  RESULTS
  HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P < .01), with HDL-c inversely correlated with HIV RNA (ρ = -0.52; P < .01). Expression of genes involved in cholesterol uptake (LDLR, CD36), synthesis (HMGCR), and regulation (SREBP2, LXRA) was significantly lower in both ART-Treated and ART-Naive subjects than in HIV-Neg controls.
  
  
  CONCLUSIONS
  In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Ireland. eoinrua@gmail.com
authors.forename: Eoin R
authors.initials: ER
authors.lastname: Feeney
authors.forename: Nuala
authors.initials: N
authors.lastname: McAuley
authors.forename: Jane A
authors.initials: JA
authors.lastname: O'Halloran
authors.forename: Clare
authors.initials: C
authors.lastname: Rock
authors.forename: Justin
authors.initials: J
authors.lastname: Low
authors.forename: Claudette S
authors.initials: CS
authors.lastname: Satchell
authors.forename: John S
authors.initials: JS
authors.lastname: Lambert
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Sheehan
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D002784:Cholesterol