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Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia.
- Source :
- Cardiovascular Research; Sep2015, Vol. 107 Issue 4, p478-486, 9p
- Publication Year :
- 2015
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 107
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 109577644
- Full Text :
- https://doi.org/10.1093/cvr/cvv186