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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2017

AutorInnen: Taylor, N; Kremser, I; Auer, S; Hoermann, G; Greil, R; Haschke-Becher, E; Esterbauer, H; Kenner, L; Oberkofler, H

Titel: Hemeoxygenase-1 as a Novel Driver in Ritonavir-Induced Insulin Resistance in HIV-1-Infected Patients.

Quelle: J Acquir Immune Defic Syndr. 2017; 75(1):e13-e20



Autor/innen der Vetmeduni Vienna:

Kenner Lukas

Beteiligte Vetmed-Organisationseinheiten
Institut für Pathologie, Abteilung für Labortierpathologie


Abstract:
Hemeoxygenase-1 (HO-1) has recently been identified as a major driver of metaflammation and obesity-related insulin resistance (IR). Drug-induced IR increases cardiovascular risk within the HIV-1-infected population receiving antiretroviral therapy (ART). We therefore investigated a possible role of HO-1 in ART-induced IR.Effects of HIV-1 protease inhibitor ritonavir and integrase inhibitor raltegravir (RAL) on expression levels of HO-1 and proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNFα), chemokine (C-C motif) ligand 5 (CCL5), and monocyte chemotactic protein 1 (MCP-1), were studied in monocyte and hepatocyte cell lines. Plasma levels of HO-1 and inflammatory markers were measured in insulin-resistant and insulin-sensitive HIV-1-infected patients under ART and seronegative controls.We show that, in contrast to RAL, ritonavir treatment significantly increases mRNA expression levels of HO-1, IL-8, TNFα, CCL5, and MCP-1 in vitro in a dose-dependent manner. HO-1 plasma levels were significantly higher in insulin-resistant compared to insulin-sensitive patients on ritonavir-boosted ART (lopinavir/ritonavir group: 3.90 ± 1.15 vs 2.56 ± 1.07 ng/mL, P < 0.005 and darunavir/ritonavir group: 3.16 ± 1.37 vs 2.28 ± 1.23 U/mL, P < 0.05) and were correlated with expression levels of TNFα in individuals on ritonavir-boosted ART (lopinavir/ritonavir group: r = 0.108, P < 0.05 and darunavir/ritonavir group: r = 0.221, P < 0.05) but not in HIV-1-infected individuals receiving RAL or in seronegative controls.HIV-1-infected patients on stable ART are often faced with non-AIDS-related metabolic comorbidities, increasing their individual cardiovascular risk. Here, we provide insight into a novel mechanism of ritonavir-induced IR involving proinflammatory properties of HO-1. Our initial observations might also provide prognostic value in the future to identify patients at risk for the development type 2 diabetes mellitus.

Keywords Pubmed: Cell Line
Cytokinesanalysis
Gene Expression Profiling
HIV Infectionscomplicationsdrug therapyvirology
HIV Protease Inhibitorsadministration & dosageadverse effects
HIV-1isolation & purification
Heme Oxygenase-1analysis
Hepatocytesenzymologyimmunology
Humans
Insulin Resistance
Monocytesenzymologyimmunology
Ritonaviradministration & dosageadverse effects

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