title: MicroRNA-210, MicroRNA-331, and MicroRNA-7 Are Differentially Regulated in Treated HIV-1-Infected Individuals and Are Associated With Markers of Systemic Inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: *Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; Departments of †Hematology; ‡Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; and §Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vibe
authors.initials: V
authors.lastname: Ballegaard
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.forename: Karin K
authors.initials: KK
authors.lastname: Pedersen
authors.forename: Malene
authors.initials: M
authors.lastname: Hove
authors.forename: Simon
authors.initials: S
authors.lastname: Koplev
authors.forename: Peter
authors.initials: P
authors.lastname: Brændstrup
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein