Vascular permeability effect of adenovirus-mediated vascular endothelial growth factor gene transfer to the rabbit and rat skeletal muscle
| Autor: | Lioubov Poliakova, Mark I. Talan, Maurizio C. Capogrossi, Imre Kovesdi, Xiatong Wang |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Vascular Endothelial Growth Factor A medicine.medical_specialty Genetic Vectors Ischemia Neovascularization Physiologic Vascular permeability Hindlimb Endothelial Growth Factors Injections Intramuscular Adenoviridae Capillary Permeability chemistry.chemical_compound Internal medicine Edema Medicine Animals Protein Isoforms Rats Wistar Muscle Skeletal Lymphokines business.industry Vascular disease Vascular Endothelial Growth Factors Genetic transfer Gene Transfer Techniques medicine.disease Surgery Rats Vascular endothelial growth factor Endocrinology medicine.anatomical_structure chemistry Rabbits medicine.symptom business Cardiology and Cardiovascular Medicine Blood vessel |
| Zdroj: | The Journal of thoracic and cardiovascular surgery. 118(2) |
| ISSN: | 0022-5223 |
| Popis: | Objective: Vascular endothelial growth factor has been used in preclinical studies and phase 1 and 2 clinical trials as a potent mediator of therapeutic angiogenesis; however, its ability to enhance the vascular permeability may be a source of potential complications. The objective of this work was to evaluate the effects of the intramuscular injection of an adenovirus vector coding for the 121–amino acid form of vascular endothelial growth factor (Ad.VEGF 121 ) on vascular permeability and edema development in rabbits and rats. Methods: Different concentrations of Ad.VEGF 121 ranging from 10 5 to 10 10 plaque-forming units/mL (3 × 10 6 -3 × 10 11 particles/mL) were injected into hind limb or forelimb muscles of Wistar rats or rabbits. The size of the scrotum, the circumferences of limbs, and the concentration of vascular endothelial growth factor in the serum were measured daily after injection. Results: The injection of different concentrations of Ad.VEGF 121 into the hind limb muscles of rabbits led to a dose-dependent scrotal edema in rabbits at concentrations higher than 10 7 plaque-forming units/mL ( P = .002). The edema developed slowly, reached its maximum level 6 days after the injection, and spontaneously resolved thereafter. At concentrations higher than 10 9 plaque-forming units/mL the scrotal edema was accompanied by skin necrosis ( P = .0001). No scrotal edema was observed in rats. Conclusions: The massive species-specific scrotal edema accompanied by skin ulceration and necrosis was observed only in rabbits treated with Ad.VEGF 121 in concentrations exceeding therapeutic doses. The therapeutic doses of Ad.VEGF 121 resulted in only moderate transient scrotal edema in rabbits, suggesting that the potential for side effects of vascular endothelial growth factor therapy as a result of increased vascular permeability should not be very alarming for generally healthy patients and may not cause a significant clinical problem in the treatment of peripheral vascular diseases. (J Thorac Cardiovasc Surg 1999;118:339-47) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|