S.D. MAYANSKAYA¹, N.Z. DAVLYATSHINA¹, E.V. MAYKOVA², M.V. TIKHOMIROVA², N.N. MAYANSKAYA¹, O.A. KRAVTSOVA² 

¹Kazan State Medical University, 39 Butlerov Str., Kazan, Russian Federation, 420012

²Kazan (Volga Region) Federal University, 18 Kremlevskaya Str., Kazan, Russian Federation, 420008

Mayanskaya S.D. ― D. Med. Sc., Professor of the Department of Hospital Therapy, tel. +7-905-316-99-66, e-mail: Smayanskaya@mail.ru

Davlyatshina N.Z. ― postgraduate student of the Department of Hospital Therapy, tel. +7-900-333-92-51, e-mail: nurfiya.20@mail.ru

Tikhomirova M.V. ― student of the Department of Biochemistry and Biotechnology, tel. +7-987-228-34-66, e-mail: mary20011994@mail.ru

Maykova E.V. ― Cand. Biol. Sc., Assistant of the Department of Biochemistry and Biotechnology, tel. +7-917-917-28-63, e-mail: kazan.gen@gmail.com

Mayanskaya N.N. ― D. Med. Sc., Professor of the Department of Biochemistry, tel. +7-903-061-14-41, e-mail: nmayansk@mail.ru

Kravtsova O.A. ― Cand. Biol. Sc., Associate Professor of the Department of Biochemistry and Biotechnology, tel. +7-905-312-99-80, e-mail: okravz@yandex.ru

In 78 patients with various manifestation rate of atherosclerotic vascular disease is studied the activity of genes expression, products of which are responsible for activation of the antioxidant system AOS. An analysis of gene NQO1 expression that controls the NADP-oxidoreductase synthesis, GCLC gene whose product is involved in the synthesis of glutathione, and HMOX1 gene involved in the modification of free heme, was made. By clinicodiagnostic methods the diagnosis of multifocal atherosclerosis (MFA) (group 1) was confirmed in 48 patients, ischemic heart disease complicated by acute coronary syndrome (ACS) (group 2) ― in 15 patients, and in 15 patients ― without clinical signs of atherosclerosis, but with the presence of risk factors (RF) to develop cardiovascular disease (CVD) (group 3).Gene expression analysis was performed in the control group (10 people), which included patients of the Department of traumatology with no signs of cardiovascular disease. Significant differences in expression of gene HMOX1 in patients with multifocal atherosclerosis, acute coronary syndrome and risk factor without clinical manifestations of cardiovascular disease as compared to the control group (p=0.0000078, p=0.00299 and p=0.012267, respectively) were obtained. The relative expression level of the GCLC gene tends to be low in patients with coronary heart disease complicated by ACS. Differences in the NQO1 gene expression are statistically significant only in the group of patients with coronary heart disease complicated by acute coronary syndrome, and the presence of risk factors for CVD development without clinical signs of atherosclerosis (p=0.03506 and p=0.01331, respectively).

Key words: antioxidant system, expression of genes HMOX1, GCLC, NQO1, multifocal atherosclerosis, risk factors, acute coronary syndrome.

REFERENCES

1. Bonetti P.O., Lerman L.O., Lerman A. et al. Endothelial dysfunction. A marker of atherosclerotic risk. Arterioscler. Thromb. Vase. Biol, 2003, vol. 23, pp. 168-175.
2. Widlansky M.E., Duffy S.J., Hamburg N.M., et al. Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic. Biol. Med, 2005, vol. 38, no. 4, pp. 499-506.
3. Stocker R., Keaney J.F. Role of oxidative modifications in atherosclerosis. Physiological reviews, 2004, vol. 84, no. 4, pp. 1381-1478.
4. Polumiskov V.Yu., Mikhin V.P. et al. Antioxidants-cytoprotectors in cardiology. Kardiovask. terap. i profil, 2004, vol. 4, no. 6, pp. 66-74 (in Russ.).
5. Ishida K., Morino T., Takagi K., Sukenaga Y. Nucleotide sequence of a human gene for gluta-thione peroxidase. Nucleic Acids Res, 1987, vol. 15, p. 10051.
6. Nagornaya N.V., Chetverik N.A. Oxidative stress: influence on the human body, methods of evaluation. Zdorov’e rebenka, 2010, no. 2 (in Russ.), available at: www.mif-ua.com/archive/issue-12604/article-12762/ (accessed: 01.02.2013).
7. Todorov I.N. Mitochondria: Oxidative Stress and Mitochondrial DNA Mutations in the Development of Pathologies, Aging and Apoptosis. Ros. khim. zh, 2007, vol. L1, no. 1, pp. 93-106 (in Russ.).
8. Rahman I., Biswas S.K., Kode A. Oxidant and antioxidant balance in the airways and airway diseases. Eur. J. Pharmacol, 2006, vol. 533, no. 1-3, pp. 222-239.
9. Babior B.M., Lambeth J.D., Nauseef W. The neutrophil NADPH oxidase. Arch. Biochem. Biophys, 2002, vol. 397, pp. 342-344.
10. Livak K.J., Schmittgen T.D. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCt Method. Methods, 2001, vol. 25 (4), pp. 402-408.
11. Nakamura S., Sugiyama S., Fujioka D. et al. Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function. J. Am. Coll. Cardiol, 2003, vol. 41, pp. 539-545.
12. Martin N.J., Collier A.C., Bowen L.D. et al. Polymorphisms in the NQO1, GSTT and GSTM genes are associated with coronary heart disease and biomarkers of oxidative stress. Mutation Research, 2009, vol. 674, pp. 93-100.
13. Lee S.O., Chang Y.C., Whang K., Kim C.H., Lee I.S. Role of NAD(P)H: quinone oxidoreductase 1 on tumor necrosis factor-alpha-induced migration of human vascular smooth muscle cells 45. Cardiovascular Research, 2007, vol. 76, pp. 331-339.
14. Otterbein L.E., Bach F.H., Alam J. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Na. Med, 2000, vol. 6, pp. 422-428.
15. Yet S.F., Layne M.D., Liu X. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascu-lar remodeling. FASEB J, 2003, vol. 17, pp. 1759-1761.
16. Tebay L.E., Robertson N., Durant S.T. et al. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic. Biol. Med, 2015, pp. 108-146.
17. Fishel M.L., Wu Kh., Devlin S.M. et al. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2. Journal of Biological Chemistry, 2015, rr. 3057-3068.
18. Gipp J.J., Mulcahy R.T. Structure of the human glutamate-L-cysteine ligase catalytic (GLCLC) subunit gene. Cytogenet. Cell Genet, 2000, vol. 88, pp. 130-132.
19. Cho S., Hazama M., Urata Y. Protective role of glutathione synthesis in response to oxidized low-density lipoprotein in human vascular endothelial cells. Free Radic. Biol. Med, 1999, P. 589-602.