Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EUCOR Newsletter Année : 2012

Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4

Ariane Galaup
  • Fonction : Auteur
Elisa Gomez
Rachid Souktani
  • Fonction : Auteur
Mélanie Durand
  • Fonction : Auteur
Aurélie Cazes
  • Fonction : Auteur
Catherine Monnot
  • Fonction : Auteur
Jérémie Teillon
  • Fonction : Auteur
Sébastien Le Jan
  • Fonction : Auteur
Claire Bouleti
  • Fonction : Auteur
Gaëlle Briois
  • Fonction : Auteur
Josette Philippe
  • Fonction : Auteur
Sandrine Pons
Valérie Martin
  • Fonction : Auteur
Rana Assaly
  • Fonction : Auteur
Philippe Bonnin
Philippe Ratajczak
  • Fonction : Auteur
Anne Janin
  • Fonction : Auteur
Gavin Thurston
  • Fonction : Auteur
David M Valenzuela
  • Fonction : Auteur
Andrew J Murphy
  • Fonction : Auteur
George D Yancopoulos
  • Fonction : Auteur
Renaud Tissier
Alain Berdeaux
  • Fonction : Auteur
Bijan Ghaleh

Résumé

BACKGROUND Increased permeability, predominantly controlled by endothelial junction stability, is an early event in the deterioration of vascular integrity in ischemic disorders. Hemorrhage, edema, and inflammation are the main features of reperfusion injuries, as observed in acute myocardial infarction (AMI). Thus, preservation of vascular integrity is fundamental in ischemic heart disease. Angiopoietins are pivotal modulators of cell-cell junctions and vascular integrity. We hypothesized that hypoxic induction of angiopoietin-like protein 4 (ANGPTL4) might modulate vascular damage, infarct size, and no-reflow during AMI. METHODS AND RESULTS We showed that vascular permeability, hemorrhage, edema, inflammation, and infarct severity were increased in angptl4-deficient mice. We determined that decrease in vascular endothelial growth factor receptor 2 (VEGFR2) and VE-cadherin expression and increase in Src kinase phosphorylation downstream of VEGFR2 were accentuated after ischemia-reperfusion in the coronary microcirculation of angptl4-deficient mice. Both events led to altered VEGFR2/VE-cadherin complexes and to disrupted adherens junctions in the endothelial cells of angptl4-deficient mice that correlated with increased no-reflow. In vivo injection of recombinant human ANGPTL4 protected VEGF-driven dissociation of the VEGFR2/VE-cadherin complex, reduced myocardial infarct size, and the extent of no-reflow in mice and rabbits. CONCLUSIONS These data showed that ANGPTL4 might constitute a relevant target for therapeutic vasculoprotection aimed at counteracting the effects of VEGF, thus being crucial for preventing no-reflow and conferring secondary cardioprotection during AMI.

Dates et versions

hal-02142788 , version 1 (28-05-2019)

Identifiants

Citer

Ariane Galaup, Elisa Gomez, Rachid Souktani, Mélanie Durand, Aurélie Cazes, et al.. Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4. EUCOR Newsletter, 2012, 125 (1), pp.140--149. ⟨10.1161/CIRCULATIONAHA.111.049072⟩. ⟨hal-02142788⟩
28 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More