Delivery of nerve growth factor (NGF) gene via recombinant plasmid vector induces angiogenesis in murine ischemic hind limb


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Abstract

The development of therapeutic angiogenesis that can stimulate the formation of mature vessels is a valuable prospect for treatment of ischemic disease, and the combination of well-known angiogenic factors with other growth factors is now beginning to show promise in therapy. In our efforts to identify possible targets for therapeutic intervention using combinations of growth factors, nerve growth factor (NGF) seems to be a possible candidate. In this study we analyzed the possibility to stimulate angiogenesis via local delivery of a plasmid encoding human nerve growth factor (hNGF). We used a murine hind-limb ischemia model to assess plasmid angiogenic potential in vivo. Plasmid DNA was diluted in saline and injected into ischemic m. tibialis anterior. Blood flow restoration was analyzed by laser Doppler imaging every 7 days after surgery, and throughout the experiment we assessed total hind-limb necrosis. After animals were sacrificed, muscle samples were frozen for histological analysis. Tissue sections were stained with antibodies against endothelium marker CD31 to assess vascular density. Blood perfusion by day 7 was higher in the NGF-treated group compared to control (p = 0.01), and by day 14 animals in the NGF-treated group had perfusion 2.8 fold higher than control animals (NGF 44.62±7.68; control 16.74±5.85; р = 0.005). Vascular density in tissue samples by day 14 in NGF-treated animals was about 2-fold higher than in the control group (р<0.05).

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About the authors

MA. A Boldyreva

Russian Cardiology Research and Production Complex

Moscow, Russia

P. I Makarevich

Russian Cardiology Research and Production Complex

Moscow, Russia

L. M Rafieva

Institute of Molecular Genetics of RAS

Moscow, Russia

I. B Beloglazova

Russian Cardiology Research and Production Complex

Moscow, Russia

K. V Dergilev

Russian Cardiology Research and Production Complex

Moscow, Russia

S. V Kostrov

Institute of Molecular Genetics of RAS

Moscow, Russia

Ye. V Parfyonova

Russian Cardiology Research and Production Complex

Moscow, Russia

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