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

Abstract

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.

• Authors: Jun Jiang, Weiping Fu, Xinwen Wang, Peter H Lin, Qizhi Yao, Changyi Chen
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 87 Issue 2 Pg. 366-74 (Jul 15 2010) ISSN: 1755-3245 [Electronic] England
• PMID: 20083573 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 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

Topics

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