study of antiatherosclerotic and endothelioprotective activity of peptide agonists of EPOR/CD131 heteroreceptor
- Authors: Puchenkova O.A.1, Nadezhdin S.V.1, Soldatov V.O.2, Zhuchenko M.A.3, Korshunova D.S.2, Kubekina M.V.2, Korshunov E.N.2, Korokina L.V.1, Golubinskaya P.A.4, Kulikov A.L.1, Gureev V.V.1, Pokrovskiy V.V.1, Patrakhanov E.A.1, Lebedev P.R.1, Denisyuk T.A.5, Belyaeva V.S.1, Movchan E.A.1, Lepetukha E.I.1, Pokrovskiy M.V.1
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Affiliations:
- Belgorod State National Research University
- Institute of Gene Biology of the Russian Academy of Sciences
- Russian Research Center “Kurchatov Institute” – State Science Research Institute of Genetics
- Clinical diagnostic laboratory Voronezh Regional Clinical Ophthalmological Hospital
- Kursk State Medical University
- Issue: Vol 8, No 2 (2020)
- Pages: 100-111
- Section: Articles
- URL: https://journals.rcsi.science/2307-9266/article/view/111632
- DOI: https://doi.org/10.19163/2307-9266-2020-8-2-100-111
- ID: 111632
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Abstract
Introduction. The drugs affecting a mitochondrial dysfunction, oxidative stresses, apoptosis and inflammation of the vascular wall, have a high potential for the prevention and treatment of atherosclerotic lesions. In this regard, the use of EPOR/CD131 heteroreceptor agonists which have a similar spectrum of pharmacological effects, is one of the promising strategies in the treatment of cardiovascular diseases.
Materials and Methods. The study was carried out on 68 C57Bl/6J male mice. Atherosclerosis was simulated in transgenic animals with an endotheliospecific knockdown of the Polg gene by simulating a balloon injury and keeping on a Western diet. Then, the studied drugs were injected once every 3 days at the dose of 20 μg/kg for 27 days. On the 28-th day, the animals were euthanized and the area of atherosclerotic plaques was assessed. The gene expression associated with the processes of inflammation, antioxidant protection, apoptosis, and angiogenesis was also determined in the aortic tissues. In addition, the endothelium protective effect of peptides on primary cultures of endothelial cells of wild and transgenic Polg-D257A mice was studied.
Results. No statistically significant effect of drugs on the area of lipid infiltration have been found. However, the studied peptides have significantly reduced the expression of proinflammatory genes (iNos, Icam1, Vcam1, Sele, Il6, Tnfa), the genes associated with angiogenesis (Vegfa, Kdr, and Hif1a), the expression of proapoptic factors; they decreased the Bax/Bcl-2 ratio by more than 1.5 times. In addition, when supplemented with H2O2 in vitro, peptides dose-dependently increased endothelial cell survival.
Conclusion. The erythropoietin-based peptides can be used to improve the functional state of the vascular wall against the background of atherosclerotic lesions and have a depressing effect on pathobiological processes associated with a mitochondrial dysfunction. In addition, the studied peptides have a significant endothelial protective effect in the induction of oxidative stress in vitro.
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##article.viewOnOriginalSite##About the authors
Olesya A. Puchenkova
Belgorod State National Research University
Author for correspondence.
Email: lesya759@yandex.ru
ORCID iD: 0000-0002-7657-0937
6th year student of the Medical Institute
Russian Federation, 85, Pobeda Str., Belgorod, 308015Sergey V. Nadezhdin
Belgorod State National Research University
Email: sergey_nadezhdin@yahoo.com
ORCID iD: 0000-0002-6249-2464
Candidate of Sciences (Biology), Researcher, the Research Institute of Pharmacology of Living Systems
Russian Federation, 85, Pobeda Str., Belgorod, 308015Vladislav O. Soldatov
Institute of Gene Biology of the Russian Academy of Sciences
Email: pharmsoldatov@gmail.com
ORCID iD: 0000-0001-9706-0699
Junior Researcher
Russian Federation, 34/5, Vavilov Str., Moscow, 119334Maxim A. Zhuchenko
Russian Research Center “Kurchatov Institute” – State Science Research Institute of Genetics
Email: maksim.zhuchenko@pharmapark.ru
Candidate of Sciences (Biology), the Head of the Sector
Russian Federation, 1, Academician Kurchatov Square, Moscow, 123098Diana S. Korshunova
Institute of Gene Biology of the Russian Academy of Sciences
Email: korshunova@genebiology.ru
ORCID iD: 0000-0002-0259-7045
Junior Researcher
Russian Federation, 34/5, Vavilov Str., Moscow, 119334Marina V. Kubekina
Institute of Gene Biology of the Russian Academy of Sciences
Email: marykumy@gmail.com
ORCID iD: 0000-0002-8834-1111
postgraduate student, junior researcher at the Center for High-Precision Editing and Genetic Technologies for Biomedicine
Russian Federation, 34/5, Vavilov Str., Moscow, 119334Evgeny N. Korshunov
Institute of Gene Biology of the Russian Academy of Sciences
Email: korshunov@genebiology.ru
ORCID iD: 0000-0001-8170-4656
The head of the vivarium, junior researcher
Russian Federation, 34/5, Vavilov Str., Moscow, 119334Liliya V. Korokina
Belgorod State National Research University
Email: korokina@mail.ru
ORCID iD: 0000-0001-5402-0697
Candidate of Sciences (Medicine), Assistant Professor, Researcher, the Research Institute of Pharmacology of Living Systems
Russian Federation, 85, Pobeda Str., Belgorod, 308015Polina A. Golubinskaya
Clinical diagnostic laboratory Voronezh Regional Clinical Ophthalmological Hospital
Email: polinapigeon@gmail.com
ORCID iD: 0000-0002-1765-9042
The Head of the Clinical Diagnostic Laboratory
Russian Federation, 22, Revolution of 1905 Str., Voronezh, 394030Aleksandr L. Kulikov
Belgorod State National Research University
Email: alex-3031@yandex.ru
Researcher, Research Institute of Pharmacology of Living Systems
Russian Federation, 85, Pobeda Str., Belgorod, 308015Vladimir V. Gureev
Belgorod State National Research University
Email: produmen@yandex.ru
ORCID iD: 0000-0003-1433-1225
Doctor of Sciences (Medicine), Associate Professor, Professor of the Department of Pharmacology and Clinical Pharmacology
Russian Federation, 85, Pobeda Str., Belgorod, 308015Vladimir V. Pokrovskiy
Belgorod State National Research University
Email: vmpokrovsky@yandex.ru
ORCID iD: 0000-0003-3138-2075
5th year student of the Medical Institute
Russian Federation, 85, Pobeda Str., Belgorod, 308015Evgeniy A. Patrakhanov
Belgorod State National Research University
Email: pateval7@gmail.com
ORCID iD: 0000-0002-8415-4562
5th year student of the Medical Institute
Russian Federation, 85, Pobeda Str., Belgorod, 308015Petr R. Lebedev
Belgorod State National Research University
Email: Artkeit@yandex.ru
ORCID iD: 0000-0001-9102-3360
5th year student of the Medical Institute
Russian Federation, 85, Pobeda Str., Belgorod, 308015Tatyana A. Denisyuk
Kursk State Medical University
Email: denitatyana@yandex.ru
ORCID iD: 0000-0003-0974-4818
Doctor of Sciences (Medicine), Associate Professor of the Department of Pharmacology
Russian Federation, 3, Karl Marx Str., Kursk, 305041Veronika S. Belyaeva
Belgorod State National Research University
Email: nika.beliaeva@yandex.ru
ORCID iD: 0000-0003-2941-0241
post-graduate student of the Department of Pharmacology and Clinical Pharmacology
Russian Federation, 85, Pobeda Str., Belgorod, 308015Evgeniya A. Movchan
Belgorod State National Research University
Email: ms.movchan@mail.ru
ORCID iD: 0000-0002-6244-2563
postgraduate student of the Department of Pharmacology and Clinical Pharmacology
Russian Federation, 85, Pobeda Str., Belgorod, 308015Elizaveta I. Lepetukha
Belgorod State National Research University
Email: lisitsa007@bk.ru
postgraduate student of the Department of Pharmacology and Clinical Pharmacology
Russian Federation, 85, Pobeda Str., Belgorod, 308015Mikhail V. Pokrovskiy
Belgorod State National Research University
Email: mpokrovsky@yandex.ru
ORCID iD: 0000-0002-2761-6249
Doctor of Sciences (Medicine), Professor of the Department of Pharmacology and Clinical Pharmacology, the Head of the Research Institute of Pharmacology of Living Systems
Russian Federation, 85, Pobeda Str., Belgorod, 308015References
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