TY - JOUR

T1 - MicroRNA-210, MicroRNA-331, and MicroRNA-7 Are Differentially Regulated in Treated HIV-1–Infected Individuals and Are Associated With Markers of Systemic Inflammation

AU - Ballegaard, Vibe

AU - Ralfkiaer, Ulrik

AU - Pedersen, Karin K.

AU - Hove, Malene

AU - Koplev, Simon

AU - Brændstrup, Peter

AU - Ryder, Lars P.

AU - Madsen, Hans O.

AU - Gerstoft, Jan

AU - Grønbæk, Kirsten

AU - Nielsen, Susanne D.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - cardiovascular disease

KW - epigenetic

KW - HIV-1

KW - immune regulation

KW - inflammation

KW - microRNA

U2 - 10.1097/QAI.0000000000001191

DO - 10.1097/QAI.0000000000001191

M3 - Journal article

C2 - 27749601

AN - SCOPUS:84991455907

VL - 74

SP - e104-e113

JO - J A I D S

JF - J A I D S

SN - 1525-4135

IS - 4

ER -