title: Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia.
abstract: BACKGROUND
  Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.
  
  
  METHODS
  Twenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05).
  
  
  CONCLUSIONS
  NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs.
authors.forename: Yong-Peng
authors.initials: YP
authors.lastname: Diao
authors.forename: Feng-Kui
authors.initials: FK
authors.lastname: Cui
authors.forename: Sheng
authors.initials: S
authors.lastname: Yan
authors.forename: Zuo-Guan
authors.initials: ZG
authors.lastname: Chen
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Lian
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Guo
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D005260:Female; D006614:Hindlimb / Q000378:metabolism* / Q000473:pathology; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A
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