The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury.
Sci Rep
; 6: 22111, 2016 Feb 25.
Article
en En
| MEDLINE
| ID: mdl-26911791
ABSTRACT
Microvascular barrier dysfunction plays a major role in the pathophysiology of acute kidney injury (AKI). Angiopoietin-1, the natural agonist ligand for the endothelial-specific Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor. Here we evaluate the efficacy of a polyethylene glycol-clustered Tie2 agonist peptide, vasculotide (VT), to protect against endothelial-cell activation with subsequent microvascular dysfunction in a murine model of ischemic AKI. Renal ischemia reperfusion injury (IRI) was induced by clamping of the renal arteries for 35 minutes. Mice were treated with VT or PEGylated cysteine before IRI. Sham-operated animals served as time-matched controls. Treatment with VT significantly reduced transcapillary albumin flux and renal tissue edema after IRI. The protective effects of VT were associated with activation of Tie2 and stabilization of its downstream effector, VE-cadherin in renal vasculature. VT abolished the decline in renal tissue blood flow, attenuated the increase of serum creatinine and blood urea nitrogen after IRI, improved recovery of renal function and markedly reduced mortality compared to PEG [HR 0.14 (95% CI 0.05-0.78) P < 0.05]. VT is inexpensive to produce, chemically stable and unrelated to any Tie2 ligands. Thus, VT may represent a novel therapy to prevent AKI in patients.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Daño por Reperfusión
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Receptor TIE-2
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Lesión Renal Aguda
/
Riñón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania