Vascular permeability effect of adenovirus-mediated vascular endothelial growth factor gene transfer to the rabbit and rat skeletal muscle.
Vascular permeability effect of adenovirus-mediated vascular endothelial growth factor gene transfer to the rabbit and rat skeletal muscle.
复制标题
腺病毒介导的血管内皮生长因子基因转移至兔和大鼠骨骼肌对血管通透性的影响。
DOI：
10.1016/s0022-5223(99)70225-4
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
M. Talan
中科院分区：
文献类型：
--
作者：
L. Poliakova;Imre Kovesdi;Xiatong Wang;M. Capogrossi;M. Talan
血管内皮生长因子已被用于临床前研究和1期和2期临床试验作为治疗性血管生成的有效介质;然而，其增强血管通透性的能力可能是潜在并发症的来源。这项工作的目的是评估肌肉注射腺病毒载体编码的121-氨基酸形式的血管内皮生长因子的影响方法用不同浓度的Ad.VEGF121（105 ~ 1010空斑形成单位/mL）对兔和大鼠血管通透性和水肿的影响将3 × 10 ~（6 -3）× 10 ~（11）个微粒/mL注射于Wistar大鼠或家兔后肢或前肢肌肉内。阴囊的大小，四肢的周长，和血清中的血管内皮生长因子的浓度进行了测定，每天注射后injection.ResultsThe注射不同浓度的Ad.VEGF121到兔后肢肌肉导致剂量依赖性阴囊水肿兔在浓度高于107斑块形成单位/mL（P = .002）。水肿发展缓慢，注射后6天达到最高水平，此后自发消退。当浓度高于109空斑形成单位/mL时，阴囊水肿伴有皮肤坏死（P = 0.0001）。没有阴囊水肿观察rats.ConclusionsThe巨大的物种特异性阴囊水肿伴随皮肤溃疡和坏死，只观察到在超过治疗剂量的浓度与Ad.VEGF121治疗的兔。治疗剂量的Ad.VEGF121仅导致兔中度一过性阴囊水肿，表明血管内皮生长因子治疗由于血管通透性增加而引起的潜在副作用对于一般健康患者不应非常令人担忧，并且在外周血管疾病的治疗中可能不会引起显著的临床问题。（《胸血管外科杂志》1999;118：339-47）
ObjectiveVascular 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.VEGF121) on vascular permeability and edema development in rabbits and rats.MethodsDifferent concentrations of Ad.VEGF121ranging from 105to 1010plaque-forming units/mL (3 × 106-3 × 1011particles/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.ResultsThe injection of different concentrations of Ad.VEGF121into the hind limb muscles of rabbits led to a dose-dependent scrotal edema in rabbits at concentrations higher than 107plaque-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 109plaque-forming units/mL the scrotal edema was accompanied by skin necrosis (P = .0001). No scrotal edema was observed in rats.ConclusionsThe massive species-specific scrotal edema accompanied by skin ulceration and necrosis was observed only in rabbits treated with Ad.VEGF121in concentrations exceeding therapeutic doses. The therapeutic doses of Ad.VEGF121resulted 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)
影响因子：
37.8
作者：
S. Takeshita;L. Q. Pu;L. Stein;A. Sniderman;S. Bunting;N. Ferrara;J. Isner;J. Symes;J. Symes
通讯作者：
S. Takeshita;L. Q. Pu;L. Stein;A. Sniderman;S. Bunting;N. Ferrara;J. Isner;J. Symes;J. Symes
DOI：
10.1016/s0022-5223(98)70455-6
发表时间：
1998-01-01
影响因子：
6
作者：
Mack, CA;Patel, SR;Rosengart, TK
通讯作者：
Rosengart, TK
DOI：
10.1073/pnas.94.22.12081
发表时间：
1997-10-28
影响因子：
11.1
作者：
Cheng, SY;Nagane, M;Cavenee, WK
通讯作者：
Cavenee, WK