Induction of apoptosis and endothelin-1 secretion in primary human lung endothelial cells by HIV-1 gp120 proteins

Georgette D. Kanmogne, Charles Primeaux, Paula Grammas

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Pulmonary hypertension associated with human immunodeficiency virus (HIV) infection also involves injury to the lung endothelium. However, the pathogenesis of HIV-induced pulmonary hypertension is not known; we hypothesized that HIV or secreted viral proteins could play a role in vascular injury and the increased frequency of pulmonary hypertension observed in HIV-infected patients. Here, we report that exposure of HIV-1 gp120 proteins to primary human lung microvascular endothelial cells causes apoptosis, as assessed by TUNEL assay, Annexin-V staining, and DNA laddering. Using ribonuclease protection assay and Western blotting we find that gp120-induced apoptosis of lung endothelial cells involves a down-regulation in Bcl-xl mRNA and proteins. In addition, gp120 significantly increases secretion of the potent vasoconstrictor endothelin-1 by human lung endothelial cells. These data suggest that secreted HIV gp120 proteins induce lung endothelial cell injury and could contribute to the development of HIV-associated pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)1107-1115
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume333
Issue number4
DOIs
StatePublished - Aug 12 2005

Keywords

  • Apoptosis
  • Endothelial cell dysfunction
  • Endothelin-1
  • HIV gp120 proteins
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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