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Antiischemic properties of the Trka-receptor agonist, the nerve growth factor 4-th loop mimetic

https://doi.org/ 10.24411/2587-7836-2018-10010.

Abstract

Resume. Relevance. One of the actual problems facing modern medical science is the study of mechanisms and the search for effective ways to activate tissue neovascularization. A possible approach to the decision of this problem is the use of TrkA receptor agonists to activate angiogenesis and, as a consequence, improve the vascularization of ischemic tissues. The aim of this investigation was to study the angiogenic and antiischemic activity of the TrkA receptor agonist the nerve growth factor 4th loop dipeptide mimetic the GK-2 compound. Methods. Experiments were performed on models of hind limb ischemia and myocardial infarction in rats. The compound GK-2 (1 mg/kg) was administered intraperitoneally for 14 days. Effects were evaluated using light microscopy and two-dimensional echocardiography. Results. In the model of the hindlimb ischemia in rats, it was shown that GK-2 (1 mg/kg, i.p.) significantly enhances the vascularization of the ischemic sural muscle. The vascularization index of ischemic tissue in animals treated with GK-2 was almost 2 times higher than in control - 27794 (25218 t 35941) and 14725 (9030 t 19630), respectively (p < 0.001). According to light microscopy, the studied compound reduces the intensity of tissue damage. Under conditions of experimental myocardial infarction, the GK-2 compound reduces the pathological remodeling intensity of the heart left ventricle. Conclusion. It can be assumed that the antiischemic effect of GK-2 is associated with increased vascularization of the affected tissue, i.e. with the stimulation of angiogenesis.

About the Authors

E. S. Pekeldina
FSBI «Zakusov institute of Pharmacology»
Russian Federation


E. O. Ionova
FSBI «Zakusov institute of Pharmacology»
Russian Federation


I. A. Mirochkina
FSBI «Zakusov institute of Pharmacology»
Russian Federation


A. V. Sorokina
FSBI «Zakusov institute of Pharmacology»
Russian Federation


V. N. Stolyaruk
FSBI «Zakusov institute of Pharmacology»
Russian Federation


I. B. Tsorin
FSBI «Zakusov institute of Pharmacology»
Russian Federation


T. A. Gudacheva
FSBI «Zakusov institute of Pharmacology»
Russian Federation


S. A. Kryzhanovskii
FSBI «Zakusov institute of Pharmacology»
Russian Federation


References

1. Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci. 2001 Jan;2(1):24- 32. DOI: 10.1038/35049004

2. Bradshaw RA, Pundavela J., Biarc J., et al. NGF and proNGF: Regulation of neuronal and neoplastic responses through receptor signaling. Adv Biol Regul. 2015 May;58:16- 27. DOI: 10.1016/j.jbior.2014.11.003

3. Schenck K., Schreurs O., Hayashi K., Helgeland K. The role of nerve growth factor (NGF) and its precursor forms in oral wound healing. Int J. Mol Sci. 2017 Feb 11;18(2). pii: E386. DOI: 10.3390/ijms18020386

4. Saygili E., Kluttig R., Rana OR, et al. Age-related regional differences in cardiac nerve growth factor expression. Age (Dordr). 2012 Jun;34(3):659- 67. DOI: 10.1007/s11357-011-9262-0

5. Re tamales-Ortega R., Orystica L., Vera C., et al. Role of nerve growth factor (NGF) and miRNAs in epithelial ovarian cancer. Int J. Mol Sci. 2017 Feb 26;18(3). pii: E507. DOI: 10.3390/ijms18030507

6. Гудашева Т.А., Антипова Т.А., Константинопольский М.А., и др. Оригинальный дипептидный миметик фактора роста нервов ГК-2 избирательно активирует пострецепторные пути TrkA, не вызывая побочных действий полноразмерного нейротрофина // ДАН. - 2014. - Т. 456. - №2. - С.231- 235. DOI: 10.7868/S0869565214140254

7. Гудашева Т.А., Антипова Т.А., Середенин С.Б. Новые низкомолекулярные миметики фактора роста нервов // ДАН. - 2010. -Т.434. - №4. - С.549- 552.

8. Крыжановский С.А., Антипова Т.А., Цорин И.Б., и др. Ангиогенные эффекты димерного дипептидного миметика четвертой петли фактора роста нервов // Бюллетень экспериментальной биологии и медицины. - 2016. - Т.161. - №4. - С.503- 507.

9. Парфенова Е.В., Ткачук В.А. Терапевтический ангтогенез: достижения, проблемы, перспективы // Кардиологический вестник. - 2007. - Т2. - №2. - С.5-15.

10. Ko SH, Bandyk DF. Therapeutic angiogenesis for critical limb ischemia. Semin Vasc Surg. 2014 Mar;27(1):23- 31. DOI: 10.1053/j. semvascsurg.2014.10.001

11. Selye AI, Bajusz E., Grasso S., Mendell B. Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology. 1960 Oct;11:398- 407. DOI: 10.1177/000331976001100505

12. Lang RM, Bierig M., Devereux RB, Flachskampf FA, Foster E., Pellikka PA, Picard MH, Roman MJ, Seward J., Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations for chamber quantification: A report from the American Society of Echocardiography’s guidelines and standards committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. Journal of the American Society of Echocardiography. 2005;18:1440- 1463. DOI: 10.1016/j.echo.2005.10.005


Review

For citations:


Pekeldina E.S., Ionova E.O., Mirochkina I.A., Sorokina A.V., Stolyaruk V.N., Tsorin I.B., Gudacheva T.A., Kryzhanovskii S.A. Antiischemic properties of the Trka-receptor agonist, the nerve growth factor 4-th loop mimetic. Pharmacokinetics and Pharmacodynamics. 2018;(2):16-21. (In Russ.) https://doi.org/ 10.24411/2587-7836-2018-10010.

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ISSN 2587-7836 (Print)
ISSN 2686-8830 (Online)