Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release

Abdelali Agouni, Hadj Ahmed Mostefai, Chiarra Porro, Nunzia Carusio, Julie Favre, Vincent Richard, Daniel Henrion, M Carmen Martínez, Ramaroson Andriantsitohaina

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120 Citations (Scopus)

Abstract

Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation. Among the candidate proteins harbored by MPs, we recently showed that sonic hedgehog (Shh) is present in MPs generated from activated/apoptotic human T lymphocytes [Martínez et al., Blood (2006) vol. 108, 3012-3020]. We show here that Shh carried by MPs induces nitric oxide (NO) release from endothelial cells, triggers changes in the expression and phosphorylation of enzymes related to the NO pathway, and decreases production of reactive oxygen species. When PI3-kinase and ERK signaling were specifically inhibited, the effects of MPs were reversed. In vivo injection of MPs in mice was also able to improve endothelial function by increasing NO release, and it reversed endothelial dysfunction after ischemia/reperfusion. Silencing the effects of Shh with cyclopamine, a specific inhibitor of Shh, or siRNA, an inhibitor of the Shh receptor Patched, strongly reduced production of NO elicited by MPs. Taken together, we propose that the biological message carried by MPs harboring Shh may represent a new therapeutic approach against endothelial dysfunction during acute severe endothelial injury.
Original languageEnglish
Pages (from-to)2735-2741
Number of pages7
JournalThe FASEB Journal
Volume21
Issue number11
DOIs
Publication statusPublished - 2007

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Keywords

  • 1-Phosphatidylinositol 3-Kinase
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Electron Spin Resonance Spectroscopy
  • Endothelium, Vascular
  • Enzyme Inhibitors
  • Flow Cytometry
  • Hedgehog Proteins
  • Humans
  • Male
  • Mice
  • Microbodies
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • RNA Interference
  • Reactive Oxygen Species
  • Signal Transduction
  • T-Lymphocytes
  • Trans-Activators
  • Transfection
  • Veratrum Alkaloids
  • Microvesicles
  • NO-synthase
  • MPs
  • PI3-kinase inhibitor

Cite this

Agouni, A., Mostefai, H. A., Porro, C., Carusio, N., Favre, J., Richard, V., ... Andriantsitohaina, R. (2007). Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. The FASEB Journal, 21(11), 2735-2741. https://doi.org/10.1096/fj.07-8079com