The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

Eoin R. Feeney, Nuala McAuley, Jane A. O'Halloran, Clare Rock, Justin Low, Claudette S. Satchell, John S. Lambert, Gerald J. Sheehan, Patrick W.G. Mallon

Research output: Contribution to journalArticle

Abstract

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). 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). 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. 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.

Original languageEnglish (US)
Pages (from-to)628-637
Number of pages10
JournalUnknown Journal
Volume207
Issue number4
DOIs
StatePublished - Feb 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Feeney, E. R., McAuley, N., O'Halloran, J. A., Rock, C., Low, J., Satchell, C. S., Lambert, J. S., Sheehan, G. J., & Mallon, P. W. G. (2013). The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation. Unknown Journal, 207(4), 628-637. https://doi.org/10.1093/infdis/jis723