Dual role of vascular endothelial growth factor in hepatic ischemia-reperfusion injury
| Autor: | Yoshiyuki Nakajima, Satoru Akashi, Hiromichi Kanehiro, Takeo Nomi, Yukiyasu Kuzumoto, Takashi Mizuno, Kaoru Hamada, Yoshikazu Tsurui, Naoya Ikeda, Hisanori Kashizuka, Masayuki Sho |
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| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology medicine.medical_specialty Necrosis Angiogenesis Ischemia Pharmacology Polymerase Chain Reaction Proinflammatory cytokine chemistry.chemical_compound Mice medicine Animals Humans Transplantation biology business.industry medicine.disease Recombinant Proteins Nitric oxide synthase Vascular endothelial growth factor Mice Inbred C57BL chemistry Gene Expression Regulation Liver Reperfusion Injury biology.protein Liver function medicine.symptom Nitric Oxide Synthase business Reperfusion injury Liver Circulation |
| Zdroj: | Transplantation. 79(9) |
| ISSN: | 0041-1337 |
| Popis: | Background. Vascular endothelial growth factor (VEGF), a major angiogenic factor, mediates a variety of disease conditions through promotion of angiogenesis. It also plays a critical role as a potent proinflammatory cytokine in a variety of physiologic and pathologic immune responses. In the present study, we evaluated the expression of VEGF in hepatic warm ischemia-reperfusion (I/R) injury and examined the effect of recombinant human (rh)VEGF administration in an established murine model. Method. The expression of VEGF in the liver was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry during I/R injury using 70% partial hepatic ischemia model. The effect of rhVEGF administration on I/R injury was evaluated by measuring liver function and histology. In addition, local inducible nitric oxide synthase (iNOS) and endothelial NO synthase expressions were examined to address the underlying mechanisms. Results. The local expression of VEGF was significantly up-regulated at 2 hours after reperfusion after 60 minutes of ischemia compared with that in the naive liver. VEGF was expressed predominantly in CD1 1b + cells infiltrating into the ischemic liver. The administration ofrhVEGF had a significant protective effect on ischemic injury in the liver. This effect was associated with the up-regulation of iNOS expression in the rhVEGF-treated liver. Conclusion. We demonstrate a dual role of VEGF in hepatic warm I/R injury. Although endogenous VEGF is expressed and functional to initiate hepatic I/R injury, exogenous rhVEGF has a beneficial effect on the ischemic liver. These data may provide new insights into the role of VEGF as well as pathophysiology of hepatic I/R injury. |
| Databáze: | OpenAIRE |
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