Angiogenic effects of combined gene therapeutic construction pcDNA_VEGF165/Ang-1 in conditions of modeling chronic limb ischemia in vivo
https://doi.org/10.29235/1814-6023-2025-22-2-95-101
Abstract
The combined plasmid construct pcDNA_VEGF165/Ang-1 has a pronounced angiogenic effect under the conditions of the modeled experimental chronic insufficiency of arterial blood supply to the limb. A single local administration of pcDNA_VEGF165/Ang-1 at a dose of 100 μg into the ischemic skeletal muscle of laboratory animals starting from the 14th day after therapy stimulates the formation of microcirculatory bed vessels with a statistically significant increase in the number of capillaries. The use of the gene therapeutic substance pcDNA_VEGF165/Ang-1 allows for complete restoration of impaired blood supply in the muscles of the thigh and lower leg of the rats by the 28th day of observation, creates conditions for maintaining a long-term positive effect until the end of the experiment (42nd day) while maintaining the number of blood vessels in one muscle fiber not lower than the healthy tissue indicator.
Keywords
About the Authors
V. G. BogdanBelarus
Vasiliy G. Bogdan – D. Sc. (Med.), Professor, Academician-Secretary of the Department of Medical Sciences.
66, Nezavisimosti Ave., 220072, Minsk
T. A. Filipovich
Belarus
Tatуana A. Filipovich – Senior Researcher.
28, Akademicheskaya Str., 220072, Minsk
E. V. Fiodorova
Belarus
Ekaterina V. Fiodorova – Researcher.
28, Akademicheskaya Str., 220072, Minsk
I. P. Zhavoronok
Belarus
Irina P. Zhavoronok – Ph. D. (Biol.), Head of the Сenter research of pain.
28, Akademicheskaya Str., 220072, Minsk
A. S. Doron’kina
Belarus
Anastasiya S. Doron’kina – Researcher.
28, Akademicheskaya Str., 220072, Minsk
S. G. Lepeshko
Belarus
Stanislav G. Lepeshko – Junior Researcher.
28, Akademicheskaya Str., 220072, Minsk
S. V. Man’kovskaya
Belarus
Svetlana V. Man’kovskaya – Deputy Director for Scientific and Innovation Work.
28, Akademicheskaya Str., 220072, Minsk
References
1. Adam D. J., Beard J. D., Cleveland T., Bell J., Bradbury A. W., Forbes J. F. [et al.]. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet, 2005. vol. 366, no. 9501, pp. 1925–1934. https://doi.org/10.1016/S0140-6736(05)67704-5
2. Bogdan V. G., Lepeshko S. G. Stimulation of angiogenesis in treatment of patients with chronic arterial insufficiency of the lower limbs. Voennaya meditsina [Military medicine], 2017, no. 2, pp. 117–119 (in Russian).
3. Bogdan V. G., Doron’kina A. S., Zhavoronok I. P., Fedorova E. V., Filippovich T. A., Lepeshko S. G., Man’kovskaya S. V. Angiogenic and antinociceptive effects of the genotherapy construction pcDNA_VEGF165 in the conditions of chronic limb ischemia in an in vivo experiment. Doklady Natsional’noi akademii nauk Belarusi = Doklady of the National Academy of Sciences of Belarus, 2024, vol. 68, no. 2, pp. 138–147 (in Russian).
4. Bogdan V. G., Poleshko A. G., Misyukevich A. Yu., Smirnov A. A., Sukhoveeva S. V., Yantsevich A. V. Biological potential of a genetic engineering construction encoding the gene for the human vascular endothelium growth factor. Vestsi Natsyyanal’nai akademii navuk Belarusi. Serуya medуtsynskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2024, vol. 21, no. 2, pp. 95–103 (in Russian).
5. Kitrou Р., Karnabatidis D., Brountzos E., Katsanos K., Reppas L., Spiliopoulos S. Gene-based therapies in patients with critical limb ischemia. Expert Opinion on Biological Therapy, 2017, vol. 17, no. 4, pp. 449–456. https://doi.org/10.1080/4712598.2017.1289170
6. Giacca M., Zacchigna S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Therapy, 2012, vol. 19, no. 6, pp. 622–629. https://doi.org/10.1038/gt.2012.17
7. Mikhailichenko V. Yu., Tsaturyan A. B., Khizriev S. M., Pilipchuk A. A., Letyuk D. V., Samarin S. A. Experience with therapeutic angiogenesis in patients with non-by passable lesion of arteries of lower extremities. Tavricheskii mediko-biologicheskii vestnik [Tauride Medical and Biological Bulletin], 2022, vol. 25, no. 2, pp. 55–60.
8. Li G., Gao J., Ding P., Gao Y. The role of endothelial cell-pericyte interactions in vascularization and diseases. Journal of Advanced Research, 2025, vol. 67, pp. 269–288. https://doi.org/10.1016/j.jare.2024.01.016
9. Bogdan V. G., Doron’kina A. S., Zhavoronok I. P., Lepeshko S. G., Man’kovskaya S. V., Yantsevich A. V. Antinociceptive efficacy of using a combined plasmid construct VEGF165-ANG-1 in animals with experimental hindlimb ischemia. Khirurgiya. Vostochnaya Evropa = Surgery. Eastern Europe, 2024, vol. 13, no. 3, pp. 363–371 (in Russian).
10. Bogdan V. G., Doron’kina A. S., Zhavoronok I. P., Fedorova E. V., Filippovich T. A., Lepeshko S. G., Man’kovskaya S. V. Pathogenetic model of chronic arterial insufficiency of blood supply to a limb in an experiment. Khirurgiya. Vostochnaya Evropa = Surgery. Eastern Europe, 2024, vol. 13, no. 1, pp. 38–48 (in Russian).
Review
For citations:
Bogdan V.G., Filipovich T.A., Fiodorova E.V., Zhavoronok I.P., Doron’kina A.S., Lepeshko S.G., Man’kovskaya S.V. Angiogenic effects of combined gene therapeutic construction pcDNA_VEGF165/Ang-1 in conditions of modeling chronic limb ischemia in vivo. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2025;22(2):95-101. (In Russ.) https://doi.org/10.29235/1814-6023-2025-22-2-95-101