Angiogenesis Induced by Endothelial Nitric Oxide Synthase Gene Through Vascular Endothelial Growth Factor Expression in a Rat Hindlimb Ischemia Model
| Autor: | Hirofumi Makino, Toshio Ogihara, Yasufumi Kaneda, Ryuichi Morishita, Naotaka Hashiya, Tsunetatsu Namba, Motokuni Aoki, Masakazu Kohno, Hiromi Koike, Kazushi Murakami |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Time Factors Nitric Oxide Synthase Type III Endothelium Angiogenesis medicine.medical_treatment Gene Expression Neovascularization Physiologic Blood Pressure Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Ischemia Enos Physiology (medical) Internal medicine medicine Animals Enzyme Inhibitors biology Growth factor Gene Transfer Techniques Genetic Therapy biology.organism_classification Hindlimb Rats Up-Regulation Vascular endothelial growth factor Nitric oxide synthase Disease Models Animal NG-Nitroarginine Methyl Ester medicine.anatomical_structure Endocrinology chemistry Regional Blood Flow Immunology biology.protein Cattle Nitric Oxide Synthase Cardiology and Cardiovascular Medicine Plasmids |
| Zdroj: | Circulation. 108:2250-2257 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background— Because the mechanism of the angiogenic property of nitric oxide (NO) was not fully understood in vivo, we focused on the role of vascular endothelial growth factor (VEGF) in angiogenesis induced by endothelial NO synthase (eNOS) gene transfer. Methods and Results— After intramuscular injection of eNOS DNA into a rat ischemic hindlimb, transfection of eNOS vector resulted in a significant increase in eNOS protein 1 week after transfection. In addition, tissue concentrations of nitrite and nitrate were significantly increased in rats transfected with the eNOS gene up to 2 weeks after transfection. The increase in tissue nitrite and nitrate concentrations was completely inhibited by N G -nitro- l -arginine methyl ester (L-NAME). In contrast, serum concentrations of nitrite and nitrate and blood pressure were not changed by eNOS gene transfer. Importantly, overexpression of the eNOS gene resulted in a significant increase in peripheral blood flow, whereas L-NAME inhibited the increase in blood flow. Interestingly, basal blood flow was significantly lower in rats treated with L-NAME than in control rats. A significant increase in capillary number was consistently detected in rats transfected with the eNOS gene at 4 weeks after transfection, accompanied by a significant increase in VEGF. Moreover, administration of neutralizing anti-VEGF antibody abolished the increase in blood flow and capillary density induced by eNOS plasmid injection. Conclusions— Overall, intramuscular injection of bovine eNOS plasmid induced therapeutic angiogenesis in a rat ischemic hindlimb model, a potential therapy for peripheral arterial disease. The stimulation of angiogenesis by NO might be due to upregulation of local VEGF expression. |
| Databáze: | OpenAIRE |
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