Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. Academic Article uri icon

Overview

abstract

  • AIMS: In myocardial ischaemia, vascular endothelial growth factor (VEGF) induces permeability by activating a signalling pathway that includes VEGF receptor 2 (VEGFR2), resulting in increased oedema and inflammation and thereby expanding the area of tissue damage. In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury. METHODS AND RESULTS: To determine whether Rip2 has a role in VEGF signalling, we used cultured endothelial cells in which Rip2 was or was not inactivated. In Rip2-deficient endothelial cells, stimulation with VEGF resulted in more rapid kinetics of VEGFR2 phosphorylation than in control cells. Rip2 deficiency also enhanced VEGF-induced activation of ERK1/2, suggesting an increased propensity for endothelial permeability. In a mouse model of myocardial ischaemia, Rip2 deficiency resulted in enhanced vascular permeability, increased oedema and expanding area of myocardial damage, and markedly reduced heart function after long-term follow-up. CONCLUSION: Our results show that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. These findings indicate that Rip2 may be a promising novel therapeutic target to reduce excess vascular permeability in ischaemic heart disease.

publication date

  • June 30, 2015

Research

keywords

  • Endothelial Cells
  • Myocardial Ischemia
  • Myocardium
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases

Identity

Scopus Document Identifier

  • 84948149673

Digital Object Identifier (DOI)

  • 10.1093/cvr/cvv186

PubMed ID

  • 26130752

Additional Document Info

volume

  • 107

issue

  • 4