M.V. PLOTNIKOV^1,2, M.O. MAVLIKEEV³, I.I. SHAMSUTDINOVA¹

¹Republican Clinical Hospital of the MH of RT, 138 Orenburgsky tract, Kazan, Russian Federation, 420064

²Kazan State Medical Academy, 36 Butlerov St., Kazan, Russian Federation, 420012

³Kazan (Volga region) Federal University, 18 Kremlevskaya St., Kazan, Russian Federation, 420008

Plotnikov M.V. — Surgery of the Department of Vascular Surgery № 1, Assistant of the Department of cardiology, endovascular and cardiovascular surgery, tel. +7-917-265-19-03, e-mail: piotnikov_mv@bk.ru

Mavlikeev M.O. — Junior Researcher, tel. +7-917-265-19-03, e-mail: MOMavlikeev@kpfu.ru

Shamsutdinova I.I. — doctor of functional diagnostics, tel. +7-927-670-04-55, e-mail: ilsgum@rambler.ru

Clinical and morphological data of «Neovaskulgen» therapy in patients with peripheral arterial disease were presented. Twice repeated intramuscular injections of Neovaskulgen (according to the manufacturer’s instructions) were performed to 10 patients with ischemia IIb-III grade by Pokrovsky-Fontaine. Standart tredmill test, ankle-brachial index estimation were performed. Injured muscle biopsies taken before and 3 months after injection was histologically studied. Pain-free walking distance increase to 31.74% at 3 months and no limits to walk at six months were detected. There were ankle-brachial index increase to 64.7% at 6 months. In intact muscles therapy with Neovaskulgen leads to increase of mean cross-sectional muscle fiber area without significant angiogenic effect. In muscles with decreased capillary density this therapy leads to blood supply improvement promoting regeneration of muscles by myosatellites proliferation and increase of mean cross-sectional muscle fiber area and connective tissue degradation.

Key words: peripheral arterial disease, gene therapy, Neovaskulgen, regeneration, muscle biopsy, immunohistochemistry.

REFERENCES

1. Selvin E., Erlinger T.P. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation, 2004, vol. 10, pp. 738-43.
2. Fowkes G.R., Rudan D., Rudan I., Aboyans V. et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. The Lancet, 2013, vol. 382, pp. 1329-1340.
3. Aquino R., Johnnides Ch., Makaroun M. et al. Natural history of claudication: Long-term serial follow-up study of 1244 claudicants. J Vasc Surg, 2001, vol. 34, pp. 962-70.
4. Norgren L. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur. J. Vasc. Endovasc. Surg, 2007, vol. 45, pp. 5-67.
5. Deev R.V., Grigoryan A.S., Potapov I.V. et al. The world experience of gene therapy of ischemic diseases. Angiologiya i sosudistaya khirurgiya, 2011, no. 17(2), pp. 145-54 (in Russ.).
6. Shval’b P.G., Kalinin R.E., Gryaznov S.V. et al. Safety and efficacy of short-term gene therapy drug in patients with chronic lower limb ischemia. Kardiologiya i serdechno-sosudistaya khirurgiya, 2011, no. 4, pp. 61-66 (in Russ.).
7. Gupta R., Tongers J., Losordo D.W. Human Studies of Angiogenic Gene Therapy. Circ. Res, 2009, vol. 105, pp. 724-36.
8. Shval’b P.G., Gavrilenko A.V., Kalinin R.E. et al. The efficacy and safety of the drug “Neovaskulgen” in the treatment of patients with chronic lower limb ischemia (IIb-III phase of clinical trials). Kletochnaya transplantologiya i tkanevaya inzheneriya, 2011, no. VI(3), pp. 76-83 (in Russ.).
9. Chervyakov Yu.V., Staroverov I.N., Nersesyan E.G et al. Therapeutic angiogenesis in the treatment of patients with chronic obliterating diseases of lower limb arteries. Nearest and remote results. Angiologiya i sosudistaya khirurgiya, 2012, no. 3, pp. 19-27 (in Russ.).
10. Ishido M., Kami K., Masuhara M. Localization of MyoD, myogenin and cell cycle regulatory factors in hypertrophying rat skeletal muscles. Acta Physiol Scand, 2004, vol. 180(3), pp. 281-9.
11. Bryan B.A., Walshe T.E., Mitchell D.C. et al. Coordinated vascular endothelial growth factor expression and signaling during skeletal myogenic differentiation. Mol Biol Cell, 2008, vol. 19(3), pp. 994-1006.
12. Zentilin L., Puligadda U., Lionetti V. et al. Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction. FASEB J, 2010, vol. 24(5), pp. 1467-78.
13. Arsic N., Zacchigna S., Zentilin L. et al. Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo. M Mol Ther, 2004, vol. 10(5), pp. 844-54.
14. Brooks N.E., Myburgh K.H. Skeletal muscle wasting with disuse atrophy is multi-dimensional: the response and interaction of myonuclei, satellite cells and signaling pathways. Front Physiol, 2014, vol. 17(5), pp. 99.