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

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

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.

Full Text

Restricted Access

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

References

  1. Deveza L., Choi J., Yang F. Therapeutic Angiogenesis for Treating Cardiovascular Diseases. Theranostics 2012; 2(8): 801-14.
  2. Carmeliet P., Jain K. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473(7347): 298-307.
  3. Xu K., Cleaver O. Tubulogenesis during blood vessel formation. Semin. Cell Dev. Biol. 2011; 22(9): 993-1004.
  4. Gupta R., Tongers J., Losordo D.W. Human Studies of Angiogenic Gene Therapy. Circ. Res. 2009; 105: 724-36.
  5. Carmeliet P. VEGF gene therapy: stimulating angiogenesis or angioma-genesis. Nat. Med. 2000; 6: 1102-13.
  6. Morishita R., Aoki M., Hashiya N. et al. Therapeutic angiogenesis using hepatocyte growth factor (HGF). Curr. Gene Ther. 2004; 4: 199-206.
  7. Shimamura M., Nakagami H., Taniyama Y. et al. Gene therapy for peripheral arterial disease. Expert Opin. Biol. Ther. 2014; 14(8): 1175-84.
  8. Ono K., Matsumori A., Shioi T. et al. Enhanced expression of hepa-tocyte growth factor/c-Met by myocardial ischemia and reperfusion in a rat model. Circulation 1997; 95(11): 2552-8.
  9. Rincon M.Y., Vanden Driessche T. et al. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation. Cardiovasc. Res. 2015; 108(1): 4-20.
  10. Pospelova T.V., Bykova T.V., Zubova S.G. et al. Rapamycin induces pluripotent genes associated with avoidance of replicative senescence. Cell Cycle 2013; 12(24): 3841-51.
  11. Semina E.V., Rubina K.A., Sysoeva V.Yu. et al. Three-Dimensional Model of Biomatrix as a Method of Studying Blood Vessels and Nerve Growth in Tissue Engineering Structures. Moscow University Chemistry Bulletin 2016; 71(3): 172-7.
  12. Makarevich P., Tsokolaeva Z., Shevelev A. et al. Combined transfer of human VEGF165 and HGF genes renders potent angiogenic effect in ischemic skeletal muscle. PLoS One 2012; 7(6): e38776.
  13. Макаревич П.И., Болдырева М.А., Дергилёв К.В. и соавт. Трансплантация клеточных пластов из мезенхимальных стромальных клеток жировой ткани эффективно индуцирует ангиогенез в ишемизированных скелетных мышцах. Г ены и Клетки 2015; 10(3): 68-77.
  14. Shevchenko E., Makarevich P., Tsokolaeva Z. et al. Transplantation of modified human adipose derived stromal cells expressing VEGF165 results in more efficient angiogenic response in ischemic skeletal muscle. J. Transl. Med. 2013; 11: 138.
  15. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005; 69: 4-10.
  16. Min J.K., Lee Y.M., Kim J.H. et al. Hepatocyte Growth Factor Suppresses Vascular Endothelial Growth Factor-Induced Expression of Endothelial ICAM-1 and VCAM-1 by Inhibiting the Nuclear Factor-B Pathway. Circ. Res. 2005; 96: 300-7.
  17. De Haro J., Acin F., Lopez-Quintana A. et al. Meta-analysis of randomized, controlled clinical trials in angiogenesis: gene and cell therapy in peripheral arterial disease. Heart Vessels 2009; 24: 321-8.
  18. Deev R., Plaksa I., Bozo I. et al. Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety and Efficacy in 210 Patients with Peripheral Arterial Disease. Am. J. Cardiovasc. Drugs 2017; 17(3): 235-42.
  19. Kim J., Mirando A.C., Popel A.S. et al. Gene delivery nanoparticles to modulate angiogenesis. Adv. Drug Deliv. Rev. In press 2016.
  20. Banfi G., von Degenfeld R., Gianni-Barrera S. et al. Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J. 2012; 26: 2486-97.
  21. Makarevich P., Tsokolaeva Z., Shevelev A. et al. Combined transfer of human VEGF165 and HGF genes renders potent angiogenic effect in ischemic skeletal muscle. PLoS One 2012; 7(6): e38776.
  22. Spanholtz T.A., Theodorou P., Holzbach T. et al. Vascular endothelial growth factor (VEGF165) plus basic fibroblast growth factor (bFGF) producing cells induce a mature and stable vascular network - a future therapy for ischemically challenged tissue. J. Surg. Res. 2011; 171: 329-38.
  23. Kupatt C., Hinkel R., Pfosser A. et al. Cotransfection of vascular endothelial growth factor - A and platelet-derived growth factor-B via recombinant adeno-associated virus resolves chronic ischemic malperfusion role of vessel maturation. J. Am. Coll. Cardiol. 2010; 56: 414-22.
  24. Su H., Takagawa J., Huang Y. et al. Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart. Int. J. Cardiol. 2009; 133: 191-7.
  25. Yu J.X., Huang X.F., Lv W.M. et al. Combination of stromal-derived factor-1alpha and vascular endothelial growth factor genemodified endothelial progenitor cells is more effective for ischemic neovascularization. J. Vasc. Surg. 2009; 50: 608-16.
  26. Макаревич П.И., Рубина К.А., Дыйканов Д.Т. и соавт. Терапевтический ангиогенез с применением факторов роста: современное состояние и перспективы развития. Кардиология 2015; 9: 59-71.

Copyright (c) 2018 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies