Effects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence-associated microRNAs.

Jamie G Hijmans,Ma'Ayan V Levy,Lillian M Brewster,Whitney Reiakvam,Elizabeth Connick,Christopher A Desouza,Kelly Stockleman,Jared J Greiner,Tyler D Bammert

doi:10.14814/phy2.13647

Jamie G Hijmans, Ma'Ayan V Levy + Show 7 more

Open Access

https://doi.org/10.14814/phy2.13647

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Abstract

The aim of this study was to determine, in vitro, the effects of X4 and R5 HIV‐1 gp120 and Tat on: (1) endothelial cell senescence and (2) endothelial cell microRNA (miR) expression. Endothelial cells were treated with media without and with: R5 gp120 (100 ng/mL), X4 gp120 (100 ng/mL), or Tat (500 ng/mL) for 24 h and stained for senescence‐associated β‐galactosidase (SA‐β‐gal). Cell expression of miR‐34a, miR‐217, and miR‐146a was determined by RT‐PCR. X4 and R5 gp120 and Tat significantly increased (~100%) cellular senescence versus control. X4 gp120 significantly increased cell expression of miR‐34a (1.60 ± 0.04 fold) and miR‐217 (1.52 ± 0.18), but not miR‐146a (1.25 ± 0.32). R5 gp120 significantly increased miR‐34a (1.23 ± 0.07) and decreased miR‐146a (0.56 ± 0.07). Tat significantly increased miR‐34a (1.49 ± 0.16) and decreased miR‐146a (0.55 ± 0.23). R5 and Tat had no effect on miR‐217 (1.05 ± 0.13 and 1.06 ± 0.24; respectively). HIV‐1 gp120 (X4 and R5) and Tat promote endothelial cell senescence and dysregulation of senescence‐associated miRs.

Highlights

Human immunodeficiency virus (HIV)-1 infection is associated with an increased risk and prevalence of atherosclerotic cardiovascular disease (CVD) (Islam et al 2012; Gibellini et al 2013; Wang et al 2015)
The percentage of senescent cells was significantly in higher in cells treated with X4 gp120 (32 Æ 1%), R5 gp120 (30 Æ 3%), and Tat (30 Æ 1%) proteins compared with control untreated cells (18 Æ 2%)
The magnitude of increase in senescent cells was similar among the HIV-1 viral proteins

Summary

Introduction

Human immunodeficiency virus (HIV)-1 infection is associated with an increased risk and prevalence of atherosclerotic cardiovascular disease (CVD) (Islam et al 2012; Gibellini et al 2013; Wang et al 2015). A major factor underlying the increased CVD burden with HIV1-infection is endothelial damage and dysfunction (Subramanian et al 2012; Gibellini et al 2013). HIV-1 gp120 and transactivator of transcription (Tat) have been shown to cause endothelial dysfunction and, in turn, have been linked to CVD pathogenesis (Kline and Sutliff 2008; Wang et al 2015; Haser and Sumpio 2017).

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