Einfluss der Tie-2 modulierenden Angiopoetine-1 und -2 auf die nephroprotektiven Effekte endothelialer Vorläuferzellen im Mäusemodell des akuten ischämischen Nierenversagens

The influence of angipoetine-1 and angiopoetine-2 to the renoprotective effect of endothelial progenitor cells in mouse models

by Jörg Rinneburger
Doctoral thesis
Date of Examination:2013-03-13
Date of issue:2013-03-08
Advisor:PD Dr. Daniel Patschan
Referee:PD Dr. Daniel Patschan
Referee:Prof. Dr. Jörg Wilting
Referee:Prof. Dr. Katrin Schäfer
Referee:Prof. Dr. Rainer Mausberg
Persistent Address: http://dx.doi.org/10.53846/goediss-3750

 

 

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Abstract

English

The aim of this study was to evaluate the modulatory effects of Angiopoietin-1 and -2 (Ang-1, Ang-2) on endothelial progenitor cells in murine acute ischemic renal failure. Therefore, C57BI/6N male mices were subjected to acute renal ischemia of 40 minutes. Mice were either injected with untreated or Ang-1-/Ang-2-pretreated syngeneic murine EPCs (cell number per experiment: 0.5*106). Concentrations of Ang-1 and Ang-2 were chosen according to previously published results on the role of Ang-2 in the process of EPC mobilization. Cell injections were performed systemically after transient occlusion of the left renal pedicle post-uninephrectomy. Analyses were performed at 48 hours after surgery. Blood was collected from the mice's hearts by transdiaphragmal punction, followed by tissue collection for histology and immunhistology. Main parameters for the prevention of acute ischaemic renal failure were serum creatinine concentration and conventional histology in comparison to untreated controls. Neither Ang-1 nor Ang-2 improved the cells renoprotective capacity. Cell pretreatment with Ang-1 resulted in further postischemic deterioration, these effects were completely blockable by coincubating the cells with Ang-1 and a specific blocking peptide. Histological analysis showed aggravation of postischemic tissue damage in mice injected with Ang-1 pretreated EPCs. Immunofluorescence did not display increased postischemic homing of prelabelled (cell tracker®) untreated or Ang-1-/ Ang-2-pretreated cells. In summary, both proteins failed to stimulate renoprotective competence of EPCs in ARF, although comparable concentrations of Ang-2 had been shown to induce EPCs mobilization if applied to mice. The mechanims responsible for deleterious effects of Ang-1 need to be elucidated.
Keywords: Renal failure; colony forming unit endothelial cells; Angiopoetin; Epc; Cfuec; Arf
 
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