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...

Authors: Rübig, Eva Christina
Stypmann, Jörg
Van Slyke, Paul
Dumont, Daniel J.
Spieker, Tilmann
Buscher, Konrad
Reuter, Stefan Johannes
Görge, Tobias
Pavenstädt, Hermann
Kümpers, Philipp
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2016
Date of publication on miami:06.06.2016
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 6 (2016) 22111, 1-11
DDC Subject:610: Medizin und Gesundheit
License:CC BY-NC 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:2045-2322
URN:urn:nbn:de:hbz:6-45279724898
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-45279724898
Other Identifiers:DOI: 10.1038/srep22111
Digital documents:srep22111.pdf

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