| Targeting vascular endothelial growth factor pathway offers new possibilities to counteract microvascular disturbances during ischemia/reperfusion of the pancreas. | |
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MedLine Citation:
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PMID: 16926599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: It is of crucial importance to explore new therapeutic strategies capable of combating or even preventing pancreatic graft failure after transplantation caused by ischemia reperfusion damage. So far, the role of the hypoxia induced mediator vascular endothelial growth factor (VEGF) upon pancreatic microcirculation has not been described. Therefore the aim of this study was to investigate its influence, using the novel tyrosinekinase inhibitor PTK787/ZK222584 (PTK/ZK), upon functional capillary density (FCD), leukocyte-endothelium interaction (LEI), and macromolecular permeability (P) of normal and postischemic pancreas tissue. METHODS: Sprague-Dawley rats were anesthetized and randomly assigned to five groups (n=7/group): (a) sham, (b) ischemia/reperfusion (I/R) control, (c) I/R and PTK/ZK treatment, (d) VEGF-superfusion, (e) VEGF-superfusion and PTK/ZK-treatment. A recently established method of digital dynamic intravital epifluorescence microscopy was used for evaluating the effective microvascular permeability together with FCD and LEI. RESULTS: Comparison between sham vs. I/R shows a significant upregulation of VEGF-expression followed by deterioration of microcirculation with decreased FCD, increased P and LEI. Treatment with PTK/ZK resulted in a significant decrease of P under conditions of superfusion with VEGF as well as I/R compared to corresponding groups without treatment. CONCLUSION: VEGF plays a crucial causative role involving an increase in permeability in normal as well as in postischemic pancreatitis via tyrosinkinase receptors. VEGF seems to be partly accountable for a deterioration of FCD and an upregulation of LEI via VEGF-tyrosinekinase receptor independent mechanisms. VEGF might be a promising potential therapeutic target in order to minimize edema formation caused by I/R and pancreatitis in pancreas transplantation. |
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Authors:
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Ernst von Dobschuetz; Sebastian Meyer; David Thorn; Dieter Marme; Ulrich Theodor Hopt; Oliver Thomusch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Transplantation Volume: 82 ISSN: 0041-1337 ISO Abbreviation: Transplantation Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-08-23 Completed Date: 2006-09-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0132144 Medline TA: Transplantation Country: United States |
Other Details:
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Languages: eng Pagination: 543-9 Citation Subset: IM |
Affiliation:
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Department of General and Visceral Surgery, University of Freiburg, Freiburg, Germany. ernst@von-dobschuetz.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capillary Permeability Edema / etiology Enzyme-Linked Immunosorbent Assay Leukocytes / physiology Male Pancreas / blood supply* Rats Rats, Sprague-Dawley Reperfusion Injury / etiology, physiopathology, therapy* Vascular Endothelial Growth Factor A / analysis, antagonists & inhibitors, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Vascular Endothelial Growth Factor A |
| Comments/Corrections | |
Comment In:
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Transplantation. 2006 Aug 27;82(4):450-1
[PMID:
16926586
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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