The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation
| Autor: | Jane A. O’Halloran, Justin Low, Claudette S. Satchell, Gerald J. Sheehan, John S. Lambert, Patrick W. G. Mallon, Clare Rock, Nuala McAuley, Eoin R. Feeney |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Anti-HIV Agents CD36 HIV Infections Biology Monocytes chemistry.chemical_compound Downregulation and upregulation Internal medicine medicine ABCA1 Gene Immunology and Allergy Humans RNA Messenger Regulation of gene expression Cholesterol Monocyte Cholesterol HDL virus diseases Biological Transport Infectious Diseases Endocrinology medicine.anatomical_structure chemistry Gene Expression Regulation Cardiovascular Diseases ABCA1 Immunology LDL receptor biology.protein lipids (amino acids peptides and proteins) ATP-Binding Cassette Transporters Female ATP Binding Cassette Transporter 1 |
| Zdroj: | The Journal of infectious diseases. 207(4) |
| ISSN: | 1537-6613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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