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Nitrotyrosine impairs angiogenesis and uncouples eNOS activity of pulmonary artery endothelial cells isolated from

Ru-Jeng Teng1, Tzong-Jin Wu, C Gaston Bisig

  • 1Department of Pediatrics, Medical College of Wisconsin, Wauwatosa, Wisconsin 53226, USA.

Pediatric Research
|November 9, 2010
PubMed

Insights

Sepsis-induced nitrotyrosine (NT) impairs developing lung growth by disrupting endothelial cell function. This study shows NT perturbs angiogenesis and vasodilation in pulmonary artery endothelial cells (PAEC), suggesting a mechanism for lung injury during infection.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Biochemistry

Background:

  • Infection during lung development can impair growth.
  • Sepsis is associated with elevated plasma free nitrotyrosine (NT) levels.
  • Free NT integrates into microtubules, affecting cell function.

Purpose of the Study:

  • To investigate the hypothesis that free NT disrupts the angiogenic activity of pulmonary artery endothelial cells (PAEC) in developing lungs.
  • To examine the effects of NT on PAEC proliferation, apoptosis, tube formation, and α-tubulin assembly.
  • To assess NT's impact on nitric oxide (NO) and superoxide anion (O2) levels, and endothelial NO synthase (eNOS) activity.

Main Methods:

  • PAEC isolated from fetal lamb lungs were exposed to varying concentrations of NT.
  • Assessed were tube formation, cell proliferation, apoptosis, and α-tubulin polymerization.
  • Measured were O2 and NO levels, eNOS dimer formation, and heat-shock-protein-90 (hsp90) association with eNOS.

Main Results:

  • NT exposure decreased PAEC tube formation and increased apoptosis.
  • NT reduced NO levels and elevated NOS-dependent O2 generation.
  • NT promoted α-tubulin depolymerization and altered eNOS/hsp90 interactions.

Conclusions:

  • Increased NT during sepsis may uncouple eNOS activity, leading to oxidative stress.
  • Impaired NO signaling and increased oxidative stress contribute to disrupted angiogenesis and vasodilation in the developing lung during sepsis.
  • These findings elucidate a potential mechanism for sepsis-induced lung injury in developing lungs.

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