Adenovirus-mediated VEGF(121) gene transfer stimulates angiogenesis in normoperfused skeletal muscle and preserves tissue perfusion after induction of ischemia

Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced in normoperfused skeletal muscles. We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of v...

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Published in:Circulation (New York, N.Y.) N.Y.), 2000-08, Vol.102 (5), p.565-571
Main Authors: Gowdak, L H, Poliakova, L, Wang, X, Kovesdi, I, Fishbein, K W, Zacheo, A, Palumbo, R, Straino, S, Emanueli, C, Marrocco-Trischitta, M, Lakatta, E G, Anversa, P, Spencer, R G, Talan, M, Capogrossi, M C
Format: Article
Language:English
Subjects:
Adenoviridae
Animals
Arterioles - physiology
Capillaries - physiology
Cytomegalovirus - genetics
Endothelial Growth Factors - genetics
Femoral Artery - physiology
Gene Transfer Techniques
Genetic Therapy - methods
Genetic Vectors
Hemodynamics - physiology
Ischemia - physiopathology
Ischemia - therapy
Lymphokines - genetics
Male
Muscle, Skeletal - blood supply
Neovascularization, Physiologic
Rabbits
Rats
Rats, Wistar
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary:Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced in normoperfused skeletal muscles. We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular endothelial growth factor (AdCMV.VEGF(121)) could stimulate neovascularization in nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit secondary to surgically induced ischemia. Rabbits and rats received IM injections of AdCMV.VEGF(121), AdCMV.Null, or saline in the thigh, 4 weeks (rabbits) or 2 weeks (rats) before femoral artery removal in the injected limb. In unoperated rats, at the site of injection of AdCMV.VEGF(121), we found 96% and 29% increases in length density of arterioles and capillaries, respectively. Increased tissue perfusion (TP) to the ischemic limb in the AdCMV.VEGF(121) group was documented, as early as day 1 after surgery, by improved blood flow to the ischemic gastrocnemius muscle measured by radioactive microspheres (AdCMV.VEGF(121)=5.69+/-0.40, AdCMV.Null=2.97+/-0.50, and saline=2.78+/-0.43 mL x min(-1) x 100 g(-1), P
ISSN:0009-7322
1524-4539