P199The muscle recovery potential of vegf gene therapy in a mouse model of hindlimb ischemia

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Abstract

Aims: The purpose of therapeutic angiogenesis in ischemic disorders is to stimulate vessel growth in areas of insufficient vascularization in an attempt to increase blood supply, and thus to support the recovery of the affected tissue. Exploiting this concept, we aimed to investigate whether angiogenesis-induced by VEGF gene therapy helped skeletal muscle to recover from ischemia insult in a mouse model of hypercholesterolemia.

Methods: Hindlimb ischemia in LDLR-/-ApoB100/100 female mice (age of 6-12 months) was generated by ligation of both femoral artery and vein proximal to the origin of the deep femoral branch, followed by intramuscular injection of adenovirus encoding human VEGF-A165 or control LacZ into posterior calf muscles.

Results: Although experiencing significant necrosis on d4, AdhVEGF-A165 transduced muscles showed accelerated muscle recovery rate between d4-7 when compared to AdLacZ controls. Enhanced muscle recovery was associated with AdhVEGF-A165 induced capillary enlargement but may also have been related to satellite cell activation. However, the initial beneficial effect of VEGF gene transfer did not expedite morphological recovery of calf muscle on d30. Furthermore, a side effect of the treatment remained the induction of significant tissue edema on d4-7.

Conclusions: A short term application of VEGF could be useful for initial tissue recovery but improving a chronic situation may require a longer VEGF expression.

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