| First Author | Andersson L | Year | 2015 |
| Journal | Cardiovasc Res | Volume | 107 |
| Issue | 4 | Pages | 478-86 |
| PubMed ID | 26130752 | Mgi Jnum | J:258760 |
| Mgi Id | MGI:6120970 | Doi | 10.1093/cvr/cvv186 |
| Citation | Andersson L, et al. (2015) Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. Cardiovasc Res 107(4):478-86 |
| abstractText | 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. |
