VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice
VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice
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DOI：
10.1096/fj.07-8459com
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Vita, Giuseppe
中科院分区：
文献类型：
--
作者：
Messina, Sonia;Mazzeo, Anna;Vita, Giuseppe
血管内皮生长因子（VEGF）是生理和病理性血管生成的主要调节因子。最近有报道称，在不同的肌肉坏死实验模型中，使用重组腺相关病毒（rAV）载体递送VEGF可以减少肌肉损伤并促进肌肉再生。我们证明，肌肉内施用rAAV-VEGF改善了mdx小鼠（杜氏肌营养不良症（DMD）的模型）的病理生理学。注射后一个月，rAAV-VEGF处理的肌肉显示VEGF的表达增强及其受体VEGFR-2的免疫定位。VEGF处理的mdx小鼠显示增加的前肢力量和标准化为体重的力量。治疗减少了坏死纤维面积，增加了再生纤维面积，肌细胞生成素阳性卫星细胞和肌细胞核的数量增加，肌球蛋白重链阳性纤维的发育。只有再生区毛细血管密度增加。这项研究提供了新的证据，VEGF的有益作用，mdx小鼠，主要是由一个proregenerative和血管生成的影响。它开辟了DMD和其他类型肌肉疾病的新治疗前景。
Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Recently it was reported that the delivery of VEGF using recombinant adeno-associated virus (rAAV) vectors reduces muscle damage and promotes muscle regeneration in different experimental models of muscle necrosis. We demonstrate that intramuscular administration of rAAV-VEGF improved pathophysiology of the mdx mouse, a model of Duchenne muscular dystrophy (DMD). One month after injection, rAAV-VEGF-treated muscles showed augmented expression of VEGF and immunolocalization of its receptor, VEGFR-2. VEGF-treated mdx mice showed increased forelimb strength and strength normalized to weight. Treatment reduced necrotic fibers area and increased regenerating fibers area with an augmented number of myogenin-positive satellite cells and myonuclei, and of developmental myosin heavy chain-positive fibers. Only the regenerating area showed increased capillary density. This study provides novel evidence of a VEGF beneficial effect in mdx mice that is exerted mainly by a proregenerative and angiogenic effect. It opens new therapeutic prospectives in DMD and other types of muscular disorders.