Dysregulation of sterol regulatory element-binding protein 2 gene in HIV treatment-experienced individuals


Autoři: Anuoluwapo Sopeyin aff001;  Lei Zhou aff001;  Min Li aff001;  Lydia Barakat aff002;  Elijah Paintsil aff001
Působiště autorů: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America aff001;  Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America aff002;  Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America aff003;  School of Public Health, Yale University, New Haven, Connecticut, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226573

Souhrn

Although antiretroviral therapy (ART) has resulted in a marked decrease in AIDS-related morbidity and mortality, the therapeutic benefit is often limited by side effects such as metabolic derangement such as lipodystrophy and hyperlipidemia and cardiovascular diseases. These side effects are pervasive in people living with HIV (PLWH). However, the underlying mechanisms are not completely understood. We investigated the effects of ART on cholesterol biosynthesis genes. This is a retrospective analysis of data and specimens collected during a cross-sectional, case-control study of ART-induced toxicity. Cases were HIV treatment-experienced individuals with HIV viral suppression and no diagnosis of ART-associated toxicity (n = 18), and controls were HIV-uninfected individuals (n = 18). The mRNA expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and ATP binding cassette transporter A1 (ABCA1) were significantly upregulated in cases (HIV+) compared to controls (HIV-), as well as the corresponding protein expression level of HMGCR. We observed dysregulation between sterol regulatory element-binding protein 2 (SREBP-2, sensory control) and HMGCR and low-density lipoprotein receptor (LDLR) pathways. Dysregulation of cholesterol biosynthesis genes may predate clinical manifestation of ART-induced lipid abnormalities.

Klíčová slova:

Biosynthesis – Gene expression – Cholesterol – Protein expression – Viral gene expression – Sterols


Zdroje

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2019 Číslo 12