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

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.