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 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 nine uninfected controls microarray profiling was performed using peripheral blood mononuclear cells (PBMC). Differentially regulated miRNAs previously related to inflammation and CVD were validated using real-time quantitative PCR (qRT-PCR) in 26 HIV-1-infected individuals and 20 uninfected controls. Validated miRNAs were measured in PBMC, CD4 and CD8 T-cells. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), high-sensitivity CRP, lipopolysaccharide (LPS), CMV IgG, lipids, and fasting glucose were measured, and associations with validated miRNAs were assessed by multiple linear regression analysis.RESULTS: Upregulation of miR-210, miR-7, and miR-331 was found in PBMC from HIV-1-infected individuals when compared to 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 TNFα (P=0.004). miR-7 in PBMC was positively associated with IL-6 (P=0.025) and fasting glucose (P=0.005), while miR-331 was negatively associated with LPS (P=0.006). In PBMC from HIV-1-infected individuals with low CMV IgG, miR-7, miR-29a, miR-221, and miR-222 were downregulated.CONCLUSION: In two 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 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 nine uninfected controls microarray profiling was performed using peripheral blood mononuclear cells (PBMC). Differentially regulated miRNAs previously related to inflammation and CVD were validated using real-time quantitative PCR (qRT-PCR) in 26 HIV-1-infected individuals and 20 uninfected controls. Validated miRNAs were measured in PBMC, CD4 and CD8 T-cells. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), high-sensitivity CRP, lipopolysaccharide (LPS), CMV IgG, lipids, and fasting glucose were measured, and associations with validated miRNAs were assessed by multiple linear regression analysis.RESULTS: Upregulation of miR-210, miR-7, and miR-331 was found in PBMC from HIV-1-infected individuals when compared to 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 TNFα (P=0.004). miR-7 in PBMC was positively associated with IL-6 (P=0.025) and fasting glucose (P=0.005), while miR-331 was negatively associated with LPS (P=0.006). In PBMC from HIV-1-infected individuals with low CMV IgG, miR-7, miR-29a, miR-221, and miR-222 were downregulated.CONCLUSION: In two 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.
U2 - 10.1097/QAI.0000000000001191
DO - 10.1097/QAI.0000000000001191
M3 - Journal article
C2 - 27749601
SN - 1525-4135
VL - 74
SP - e104-e113
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
IS - 4
ER -