MicroRNA-210, MicroRNA-331, and MicroRNA-7 Are Differentially Regulated in Treated HIV-1–Infected Individuals and Are Associated With Markers of Systemic Inflammation
| Autor: | Karin K. Pedersen, Kirsten Grønbæk, Susanne Dam Nielsen, Hans O. Madsen, Vibe Ballegaard, Lars P. Ryder, Simon Koplev, Peter Braendstrup, Ulrik Ralfkiaer, Malene Hove, Jan Gerstoft |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine HIV Infections Inflammation Biology Systemic inflammation Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation microRNA medicine Humans Cytotoxic T cell Pharmacology (medical) 030212 general & internal medicine Tumor Necrosis Factor-alpha Gene Expression Profiling Reproducibility of Results Middle Aged Viral Load MicroRNA 7 MicroRNAs C-Reactive Protein 030104 developmental biology Infectious Diseases Immunology HIV-1 Female Tumor necrosis factor alpha medicine.symptom Biomarkers |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 74:e104-e113 |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/qai.0000000000001191 |
| Popis: | OBJECTIVE Inflammation may contribute to an increased risk of cardiovascular disease (CVD) in HIV-1 infection. MicroRNAs (miRNAs) are involved in the regulation of inflammation. In treated HIV-1-infected individuals, we aimed to identify differentially expressed miRNAs with known roles in inflammation and CVD risk and to investigate associations between these and systemic inflammation. METHODS In a screening cohort including 14 HIV-1-infected individuals and 9 uninfected controls, microarray profiling was performed using peripheral blood mononuclear cells (PBMCs). Differentially regulated miRNAs previously related to inflammation and CVD were validated using real-time quantitative reverse-transcription polymerase chain reaction in 26 HIV-1-infected individuals and 20 uninfected controls. Validated miRNAs were measured in PBMCs, CD4 and CD8 T cells. Interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, lipopolysaccharide (LPS), cytomegalovirus immunoglobulin G, lipids, and fasting glucose were measured, and associations with validated miRNAs were assessed with multiple linear regression analysis. RESULTS Upregulation of miR-210, miR-7, and miR-331 was found in PBMCs from HIV-1-infected individuals when compared with those from uninfected controls (P < 0.005). In contrast, miR-210 and miR-331 were downregulated in CD8 T cells. In multivariate analysis, miR-210 in CD8 T cells was negatively associated with LPS (P = 0.023) and triglycerides (P = 0.003) but positively associated with tumor necrosis factor-alpha (P = 0.004). MiR-7 in PBMC was positively associated with interleukin-6 (P = 0.025) and fasting glucose (P = 0.005), whereas miR-331 was negatively associated with LPS (P = 0.006). In PBMCs from HIV-1-infected individuals with low cytomegalovirus immunoglobulin G, miR-7, miR-29a, miR-221, and miR-222 were downregulated. CONCLUSION In 2 independent cohorts, miR-210, miR-7, and miR-331 were differentially regulated in treated HIV-1-infected individuals and associated with markers of systemic inflammation. |
| Databáze: | OpenAIRE |
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