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. 2023 Jan;174(3):333-336.
doi: 10.1007/s10517-023-05703-7. Epub 2023 Feb 1.

Anti-Atherosclerotic Action of a New Stimulator of Soluble Guanylate Cyclase in an Experiment

V V Bykov  1   2 , A V Bykova  3 , A N Dzyuman  4 , V V Ivanov  4 , V A Khazanov  3 , A I Vengerovskii  4 , V V Udut  5
Affiliations

Anti-Atherosclerotic Action of a New Stimulator of Soluble Guanylate Cyclase in an Experiment

V V Bykov et al. Bull Exp Biol Med. 2023 Jan.

Abstract

We studied the effect of an indolinone derivative GRS on the development of experimental atherosclerosis in C57BL/6 mice. Atherosclerosis was modeled by intraperitoneal administration of endothelial lipoprotein lipase inhibitor Kolliphor P 407 micro Geismar over 5 months. GRS was administered orally in a dose of 10 mg/kg once a day throughout the experiment. In 5 months, the levels of total cholesterol, LDL, and triglycerides in blood serum, as well as histological composition of the ascending aorta were studied. In mice with experimental atherosclerosis, we observed pronounced dyslipidemia with an increase in serum cholesterol, LDL, and triglycerides and accumulation of xanthoma cells in the aorta wall. Repeat administration of GRS did not eliminate dyslipidemia, but prevented an increase in the number of xanthoma cells in the aorta wall (p<0.05). The stimulator of soluble guanylate cyclase GRS did not exhibit hypolipidemic activity, but restored impaired endothelial function in the atherosclerosis model and prevented atherosclerotic damage to blood vessels and vascular wall remodeling.

Keywords: endothelial dysfunction; experimental model of atherosclerosis; indolinone derivative; soluble guanylate cyclase stimulator; xanthoma cells.

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References

    1. Russia in Figures 2019: Statistical Handbook. Moscow, 2019. Russian.
    1. Kukharchuk VV, Ezhov MV, Sergienko IV, Arabidze GG, Bubnova MG, Balakhonova TV, Gurevich VS, Kachkovsky MA, Konovalov GA, Konstantinov VO, Malyshev PP, Pokrovsky SN, Sokolov AA, Sumarokov AB, Gornyakova NB, Obrezan AG, Shaposhnik II, Ansheles AA, Aronov DM, Akhmedzhanov NM, Barbarash OL, Boitsov SA, Voevoda MI, Galstyan GR, Galyavich AS, Drapkina OM, Duplyakov DV, Karpov RS, Karpov YuA, Koziolova NA, Nebieridze DV, Nedogoda SV, Oleinikov VE, Ragino YuI, Skibitsky VV, Smolenskaya OG, Filippov AE, Khalimov YuSh, Chazova IE, Shestakova MV, Yakushin SS. Diagnostics and correction of lipid metabolism disorders in order to prevent and treat atherosclerosis. Russian recommendations, VII revision. Ateroskleroz Dislipidemiya. 2020;(1):7-40. Russian. doi: https://doi.org/10.34687/2219-8202.JAD.2020.01.0002
    1. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23, Suppl 1):III27-III 32. doi: https://doi.org/10.1161/01.CIR.0000131515.03336.f8
    1. Makhoul S, Walter E, Pagel O, Walter U, Sickmann A, Gambaryan S, Smolenski A, Zahedi RP, Jurk K. Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets. Nitric Oxide. 2018;76:71-80. doi: https://doi.org/10.1016/j.niox.2018.03.008 - DOI
    1. Bykov VV, Smol’yakova VI, Chernysheva GA, Aliev OI, Anishchenko AM, Sidekhmenova AV, Dunaeva OI, Stankevich SA, Khazanov VA. Effects of a New Antithrombotic Drug GRS, a Soluble Guanylate Cyclase Stimulator, on Endothelial Dysfunction in Rats with Myocardial Infarction. Bull. Exp. Biol. Med. 2022;172(6):709-712. doi: https://doi.org/10.1007/s10517-022-05461-y

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