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The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury

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.

Titel: The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury
Verfasser: Rübig, Eva Christina GND
Stypmann, Jörg
Van Slyke, Paul
Dumont, Daniel J.
Spieker, Tilmann
Buscher, Konrad GND
Reuter, Stefan Johannes GND
Görge, Tobias GND
Pavenstädt, Hermann
Kümpers, Philipp GND
Organisation: FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 25.02.2016
Publikation in MIAMI: 06.06.2016
Datum der letzten Änderung: 16.09.2016
Quelle: Scientific Reports 6 (2016) 22111, 1-11
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY-NC 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-45279724898
Permalink: http://nbn-resolving.de/urn:nbn:de:hbz:6-45279724898
DOI: 10.1038/srep22111
ISSN: 2045-2322
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