Features of the relationship between clinical and laboratory, ultrasound signs of atherosclerosis and antioxidant defense in patients with comorbid pathology


DOI: https://dx.doi.org/10.18565/therapy.2021.9.76-84

Polyakov V.Ya., Kovrigin I.I., Kozhin P.M., Nikolaev Yu.A., Malov A.S., Sevostyanova E.V., Menschikova E.B.

Federal Research Center for Fundamental and Translational Medicine, Novosibirsk
Abstract. The ambiguity of data on Nrf2-mediated redox-sensitive signaling pathways participation in atherogenesis and the progression of atherosclerosis determines the need to search for new data on the mechanisms of cause-effect relationships of these processes.
The aim of the research was to study the features of clinical and laboratory markers of atherosclerosis and the level of genes expression of the antioxidant defense system (NRF2, HMOX1, NQO1, GSTP1) in correlation to the echoscopically verified degree of carotid artery (CA) stenosis.
Material and methods. The study included 160 patients from the clinic of the Federal research center for fundamental and translational Medicine aged from 35 to 78 years. They underwent clinical and laboratory diagnostics, ultrasound examination of brachiocephalic arteries, assessment of the expression of genes involved in the formation of antioxidant protection (NRF2, NQO1, HMOX1, GSTP1) using RT-PCR methodic.
Results. It was found that in peripheral blood leukocytes of patients with verified CA atherosclerosis, the expression of GSTP1, NQO1, and NRF2 genes is reduced (by 49, 51, and 44%, respectively), while the mRNA contained amount of the HMOX1 gene is not changed. A correlation was revealed between the severity of expression of genes GSTP1, HMOX1, NQO1, NRF2, indicators of blood lipid spectrum, as well as the degree of CA stenosis: an inverse correlation between the expression of NQO1 gene and the percentage of stenosis in the left common CA, expression of GSTP1 gene and the atherogenic coefficient, a direct relationship between the level of mRNA of the NRF2 gene and the concentration of high density lipoproteins (HDL). A direct correlation was found between the concentration of triglycerides and the thickness of the «intima-media» complex, the content of total cholesterol and the blood flow rate in the right internal CA, an inverse correlation between the level of HDL, as well as the concentration of apolipoprotein A and the thickness of the «intima-media» complex of the common CA.
Conclusion. Complex pathogenetic interrelationships of the expression of antioxidant defense genes, the degree of atherosclerotic stenosis and blood flow velocity of CA, as well as indexes of blood lipid spectrum are shown.
Keywords: polymorbidity scale, ultrasound scanning of arteries, antioxidant defense system, blood lipid spectrum, atherosclerosis, gene expression
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About the Autors

Vladimir Ya. Polyakov, MD, leading researcher of the laboratory of somatic diseases pathogenesis of the Department of biomedical research, Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25. E-mail: vpolyakov15@mail.ru. ORCID: 0000-0002-9606-2331
Igor I. Kovrigin, resident in «Therapy» specialty of Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (913) 797-73-26. E-mail: ahilles9@bk.ru
Petr M. Kozhin, PhD, senior researcher of the Laboratory of molecular mechanisms of free radical processes of the Department of general pathology, Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. E-mail: kozhinpm@centercem.ru. ORCID: 0000-0002-9989-9778
Yuri A. Nikolaev, MD, head of the Laboratory of pathogenesis of somatic diseases of the Department of biomedical research, Federal Research Center for Fundamental and Translational Medicine, chief researcher. Address: 630117, Novosibirsk, 2 Timakova Str. E-mail: nicol@centercem.ru. ORCID: 0000-0002-1690-6080
Alexander S. Malov, resident in «Therapy» specialty of Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Stк. Tel.: +7 (996) 376-58-00. E-mail: malov_as@cnmt.ru
Evgeniya V. Sevostyanova, PhD, senior researcher of the Laboratory of pathogenesis of somatic diseases of the Department of biomedical research, Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (913) 897-49-68. E-mail: luck.nsk@rambler.ru. ORCID: 0000-0003-1132-3801
Elena B. Menshchikova, MD, head of the Laboratory of molecular mechanisms of free-radical processes of the Department of general pathology, Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. E-mail: lemen@centercem.ru. ORCID: 0000-0003-2367-0114


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