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HIV‐1 Infection and Inflammation‐Related microRNAs
Author(s) -
Hijmans Jamie,
Levy Ma'ayan,
Greiner Jared,
Stauffer Brian,
Connick Elizabeth,
DeSouza Christopher
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1015.33
Subject(s) - inflammation , microrna , disease , immunology , medicine , human immunodeficiency virus (hiv) , pathological , biology , gene , genetics
microRNAs (miRs) are short single stranded noncoding RNAs that are involved in the regulation of a number of physiological and pathological processes. miRs down regulate target gene expression post‐transcriptionally by degrading messenger RNA and/or by blocking translation. It is now recognized that miRs play a key role in regulating inflammatory processes underlying cardiovascular disease (CVD). For example, altered expression of specific miRs, such as, miR‐126, miR‐146a, miR‐150 and miR‐34a have been linked with heightened vascular inflammation, atherosclerosis and CVD risk. Human immunodeficiency virus (HIV)‐1 is associated with increased vascular inflammation and that is thought to contribute to greater CVD risk. The mechanisms underlying the heightened HIV‐1‐related inflammatory stress are not fully understood. It is currently unknown whether inflammation‐related miRs are dysregulated with HIV‐1‐infection. Accordingly, the aim of this study was to determine the influence of HIV‐1‐infection, independent of other risk factors, on circulating expression of miR‐34a, miR‐126, miR‐146a and miR‐150. A total of 25 sedentary, middle‐aged adults have been studied: 10 HIV‐1‐seronegative adults (8M/2F; age 37±4 yr; BMI: 24.6±3 kg/m 2 ) and 15 HIV‐1‐seropositive adults on stable antiretroviral therapy (11M/4F; age 38±3 yr; BMI:25.0±3 kg/m 2 ). All subjects were non‐obese, normotensive, normolipidemic, and free of overt cardiometabolic disease. Circulating expression of miRs was determined in plasma using standard RT‐PCR techniques with miR primers of interest. Expression was normalized to exogenous C. elegans miR‐39 and reported as relative expression in arbitrary units (AU). Circulating expression of anti‐inflammatory miRs: miR‐126 (0.36±.015 vs 1.16±0.45 AU), miR‐146a (0.75±0.27 vs 4.20±1.90 AU) and miR‐150 (0.19±0.0 vs 3.50±1.43AU) were markedly lower (~70%, 85%, and 95% respectively; P<0.05) in the HIV‐1‐seropositive group compared with the HIV‐1‐seroponegative group. Moreover, the pro‐inflammatory miR‐34 (0.5±0.25 vs 1.30±0.60 AU) was ~60% higher in the HIV‐1‐seropositive group compared with the HIV‐1‐seronegative groups. Lower expression of miR‐126, miR‐146a and miR‐150 is consistent with a proinflammatory and proatherogenic phenotype, as they are involved in limiting inflammatory pathways. In summary, these results suggest that dysregulation of key inflammation‐related miRs may underlie and promote the heightened inflammatory state associated with HIV‐1‐infection in adults.