Efficacy of combined use of plasmid constructs containing HGF and angiopoietin-1 genes to restore blood flow in ischemic tissues

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Abstract

New methods to stimulate blood supply of the ischemic organs and tissues are being intensively developed worldwide. These approaches are based on revascularization and remodeling of the newly formed blood vessels. This strategy was called therapeutic angiogenesis. Using in vitro, ex vivo and in vivo models we investigated the specific biological activity and angiogenic potential of Vascopoietin, which contained the plasmids for HGF and angiopoietin-1 expression. Vascopoietin stimulated vascular cell migration, proliferation and the formation of capillary-like structures in vitro and ex vivo. Using in vivo model of posterior limb ischemia in mice we demonstrated that Vascopoietin administration mediated stable HGF and angiopoietin-1 production resulting in new blood vessel formation and their stabilization in the ischemic muscles. In addition, Vascopoietin injection led to the restoration of the blood flow, decrease in the size of necrosis in ischemic limb and the reduction in the amputation frequency. The current data suggest Vascopoietin a promising drug for therapeutic angiogenesis.

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About the authors

KA. A Rubina

M.V. Lomonosov Moscow State University

E. V Semina

M.V. Lomonosov Moscow State University; Russian Cardiology Research and Production Complex

Email: e-semina@yandex.ru

D. T Diykanov

M.V. Lomonosov Moscow State University

M. A Boldyreva

Russian Cardiology Research and Production Complex

P. I Makarevich

Russian Cardiology Research and Production Complex; Institute of Regenerative Medicine, Medical Research and Education Centre, M.V. Lomonosov Moscow State University

Y. V Parfyonova

M.V. Lomonosov Moscow State University; Russian Cardiology Research and Production Complex

Zh. A Akopyan

M.V. Lomonosov Moscow State University; Institute of Regenerative Medicine, Medical Research and Education Centre, M.V. Lomonosov Moscow State University

VA. A Tkachuk

M.V. Lomonosov Moscow State University; Russian Cardiology Research and Production Complex; Institute of Regenerative Medicine, Medical Research and Education Centre, M.V. Lomonosov Moscow State University

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