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Article Dans Une Revue Arteriosclerosis, Thrombosis, and Vascular Biology Année : 2019

Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis

Mélissande Cossutta
Marie Darche
  • Fonction : Auteur
Gilles Carpentier
  • Fonction : Auteur
Claire Houppe
  • Fonction : Auteur
Matteo Ponzo
  • Fonction : Auteur
Fabio Raineri
  • Fonction : Auteur
Benoit Vallée
  • Fonction : Auteur
Maud-Emmanuelle Gilles
  • Fonction : Auteur
Delphine Villain
  • Fonction : Auteur
Émilie Picard
Caterina Casari
Cécile Denis
Michel Paques
  • Fonction : Auteur
José Courty
Ilaria Cascone
  • Fonction : Auteur

Résumé

Weibel-Palade bodies (WPBs) are endothelial cell (EC)-specific organelles formed by vWF (von Willebrand factor) polymerization and that contain the proangiogenic factor Ang-2 (angiopoietin-2). WPB exocytosis has been shown to be implicated for vascular repair and inflammatory responses. Here, we investigate the role of WPBs during angiogenesis and vessel stabilization. APPROACH AND RESULTS: WPB density in ECs decreased at the angiogenic front of retinal vascular network during development and neovascularization compared with stable vessels. In vitro, VEGF (vascular endothelial growth factor) induced a VEGFR-2 (vascular endothelial growth factor receptor-2)-dependent exocytosis of WPBs that contain Ang-2 and consequently the secretion of vWF and Ang-2. Blocking VEGF-dependant WPB exocytosis and Ang-2 secretion promoted pericyte migration toward ECs. Pericyte migration was inhibited by adding recombinant Ang-2 or by silencing Ang-1 (angiopoietin-1) or Tie2 (angiopoietin-1 receptor) in pericytes. Consistently, in vivo anti-VEGF treatment induced accumulation of WPBs in retinal vessels because of the inhibition of WPB exocytosis and promoted the increase of pericyte coverage of retinal vessels during angiogenesis. In tumor angiogenesis, depletion of WPBs in vWF knockout tumor-bearing mice promoted an increase of tumor angiogenesis and a decrease of pericyte coverage of tumor vessels. By another approach, normalized tumor vessels had higher WPB density. CONCLUSIONS: We demonstrate that WPB exocytosis and Ang-2 secretion are regulated during angiogenesis to limit pericyte coverage of remodeling vessels by disrupting Ang-1/Tie2 autocrine signaling in pericytes. VISUAL OVERVIEW: An online visual overview is available for this article.

Dates et versions

hal-03095533 , version 1 (14-02-2024)

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Citer

Mélissande Cossutta, Marie Darche, Gilles Carpentier, Claire Houppe, Matteo Ponzo, et al.. Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 2019, 39 (9), pp.1843-1858. ⟨10.1161/ATVBAHA.119.313021⟩. ⟨hal-03095533⟩
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