HIV gp120 induces endothelial dysfunction in tumour necrosis factor-alpha-activated porcine and human endothelial cells

Cardiovasc Res. 2010 Jul 15;87(2):366-74. doi: 10.1093/cvr/cvq013. Epub 2010 Jan 18.


Aims: The aim of this study was to determine direct effects and potential molecular mechanisms of HIV gp120, a viral envelope glycoprotein, on endothelial function.

Methods and results: Fresh porcine coronary artery rings and human coronary artery endothelial cells (HCAECs) were treated with recombinant HIV gp120 for 16 h with or without pretreatment with tumour necrosis factor-alpha (TNF-alpha) (8 h). With a myograph tension analysis, HIV gp120 with TNF-alpha pretreatment significantly decreased endothelium-dependent vasorelaxation in response to bradykinin in porcine coronary artery rings compared with untreated control vessels. In addition, HIV gp120 with TNF-alpha pretreatment significantly reduced endothelial nitric oxide synthase (eNOS) expression-both mRNA and protein levels-in porcine coronary artery rings and HCAECs compared with untreated controls. Furthermore, TNF-alpha pretreatment substantially increased intercellular adhesion molecule-1 (ICAM-1) expression in artery rings and HCAECs. Anti-gp120 or anti-ICAM-1 antibody significantly blocked these effects of HIV gp120. Silencing of ICAM-1 by siRNA oligonucleotides significantly blocked the effect of gp120 on eNOS downregulation in TNF-alpha-pretreated HCAECs.

Conclusion: HIV gp120 and TNF-alpha synergistically reduce eNOS expression and cause endothelial dysfunction in both porcine coronary arteries and HCAECs. ICAM-1 induced by TNF-alpha pretreatment may mediate HIV gp120-induced endothelial dysfunction, which suggests a novel molecular mechanism of HIV gp120-ICAM-1 interaction inducing endothelial dysfunction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • HIV Envelope Protein gp120 / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • RNA Interference
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Swine
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology


  • HIV Envelope Protein gp120
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Intercellular Adhesion Molecule-1
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Bradykinin