VEGF-A blockade reduces reperfusion edema but favors arterial thromboembolism in a rat model of orthotopic lung transplantation
| Autor: | Bertram Scheller, Kai Zacharowski, Patrick Paulus, Pia Ockelmann, Christin Reissig, Johannes Holfeld, Anja Urbschat, Elisabeth Tybl |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Time Factors medicine.medical_treatment Organ Preservation Solutions Urology Inflammation Apoptosis Rats Sprague-Dawley chemistry.chemical_compound Edema Thromboembolism medicine Lung transplantation Animals Hypoxia Transplantation business.industry Thrombosis Arteries medicine.disease Blockade Rats Vascular endothelial growth factor Blot Disease Models Animal Cytokine Phenotype chemistry Anesthesia Reperfusion Injury medicine.symptom business Proto-Oncogene Proteins c-akt Lung Transplantation |
| Zdroj: | Transplantation. 97(9) |
| ISSN: | 1534-6080 |
| Popis: | BACKGROUND Ischemia-reperfusion edema is a common early complication after lung transplantation where the hypoxia-induced vascular endothelial growth factor (VEGF)-A plays a pivotal role. It remains unclear whether a VEGF blockade is beneficial in lung transplantation. METHODS VEGF-A blockade was investigated in an orthotopic rat model of lung transplantation. VEGF-A antibody was added into the preservation solution alone (α-VEGF D/-), in the preservation solution and systemically to the recipient before reperfusion (α-VEGF D/R), or applied to the recipient alone before reperfusion (α-VEGF -/R). Forty-eight hours after lung transplantation, left lungs were collected and wet-to-dry ratio, Western blotting, RT-PCR, and immunohistology were performed. RESULTS VEGF-A blockade in α-VEGF D/-, α-VEGF D/R, and α-VEGF -/R resulted in neutralization of tissue VEGF-A. Reperfusion edema was only reduced in α-VEGF D/R and α-VEGF D/- groups versus Perfadex controls. Some α-VEGF -/R rats showed a hyperinflammation leading to increased pro-inflammatory cytokine expressions as well as increased edema. Whereas generally the α-VEGF D/- group showed decreased inflammation, the combination with anti-VEGF treatment to the recipient resulted in a pro-inflammatory and a pro-apoptotic phenotype. Short-term survival, however, was not significantly different in all groups as compared to the controls. In the α-VEGF (D/R) or (D/-) groups, animals mainly died from arterial thromboembolisms and in the α-VEGF (-/R) group, hyperinflammation was the main cause of death. CONCLUSION VEGF-A directly contributes to the formation of a reperfusion edema, which might be reduced by its blockade. However, the α-VEGF effect on the endothelial integrity might also favor arterial thrombosis formation. |
| Databáze: | OpenAIRE |
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