THE EFFECT OF STATIN ADMINISTRATION ON THE INFLAMMATORY RESPONSE OF MONOCYTES IN PATIENTS WITH ATHEROSCLEROSIS



Cite item

Full Text

Abstract

Abstract

Currently, statins are the main preparations of anti-atherosclerotic therapy due to a number of effects that reduce the progression of atherosclerosis, including anti-inflammatory effectiveness. The purpose of this study was to evaluate the inflammatory response of monocytes in patients with severe atherosclerosis during therapy with hydrophilic and lipophilic statins, as well as in patients with atherosclerosis not receiving lipid-lowering therapy. Materials and methods. A total of 60 patients with severe atherosclerosis of the coronary arteries were included in the study in three groups: 1) receiving atovastatin therapy for at least 12 months before inclusion in the study, n=20; 2) receiving rosuvastatin therapy for at least 12 months before inclusion in the study, n=20; 3) those who had not received statin therapy within a year before inclusion in the study, n=20. The primary culture of monocytes from study participants was obtained by gradient centrifugation followed by immunomagnetic separation of CD14+ monocytes. The isolated cells were cultured for 7 days without stimulation and with pro-inflammatory stimulation using lipopolysaccharide (LPS). The level of basal, LPS-stimulated and re-stimulated secretion of TNF-α and IL-1β was determined by enzyme immunoassay. Results. Basal secretion of TNF-α and IL-1β in patients receiving statins was lower than in patients who did not receive statins for a year; the secretion of both cytokines was significantly lower in the rosuvastatin group. LPS-stimulated TNF-α secretion was significantly lower in the groups of patients receiving statins; IL-1β secretion was significantly lower in the atorvastatin and rosuvastatin groups compared to the group without statins. Re-stimulated IL-1β secretion did not differ significantly between groups; re-stimulated TNF-α secretion was significantly lower in the rosuvastatin group compared to the atorvastatin and non-statin groups. Thus, the results of the study demonstrate the anti-inflammatory effectiveness of rosuvastatin, expressed in a decrease in the secretion of pro-inflammatory cytokines by cultured monocytes/macrophages of patients with severe coronary atherosclerosis.

About the authors

Tatiana V. Kirichenko

Petrovsky National Research Centre of Surgery, Moscow, Russia;
Chazov National Medical Research Center of Cardiology, Moscow, Russia

Email: t-gorchakova@mail.ru
ORCID iD: 0000-0002-2899-9202
SPIN-code: 4332-9045
Scopus Author ID: 55004801700
ResearcherId: R-8560-2017

Cand. Sci. (Med.), Senior Researcher, Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Centre of Surgery, Researcher, Laboratory of Medical Genetics, Chazov National Medical Research Center of Cardiology

Russian Federation, Москва, Абрикосовский пер., 2

Irina Yu. Yudina

I.M. Sechenov First Moscow State Medical University, Moscow, Russia

Email: ikozlovskaya@mail.ru
Scopus Author ID: 58072848800

Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University

Russian Federation, г. Москва, ул. Трубецкая, д.8, стр.2

Maria V. Lukina

I.M. Sechenov First Moscow State Medical University, Moscow, Russia

Email: lukina_m_v_1@staff.sechenov.ru
ORCID iD: 0000-0003-0032-2651
Scopus Author ID: 57202002278

Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sklifosovsky Institute of Clinical Medicine, clinical pharmacologist of the University Clinical Hospital No. 1, I.M. Sechenov First Moscow State Medical University

Russian Federation, г. Москва, ул. Трубецкая, д.8, стр.2

Tatyana B. Andrushchishina

I.M. Sechenov First Moscow State Medical University, Moscow, Russia

Email: andrushchishina_t_b@staff.sechenov.ru
ORCID iD: 0000-0001-7940-4443
Scopus Author ID: 6504214828

Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sklifosovsky Institute of Clinical Medicine, clinical pharmacologist of the University Clinical Hospital No. 1, I.M. Sechenov First Moscow State Medical University

Russian Federation, г. Москва, ул. Трубецкая, д.8, стр.2

Ivan V Zhivodernikov

Petrovsky National Research Centre of Surgery, Moscow, Russia

Email: kordait-2213@yandex.ru
Scopus Author ID: 57200645355

Cand. Sci. (Biol.), Researcher, Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Centre of Surgery

Russian Federation, г. Москва, Абрикосовский переулок, д.2

Yuliya V Markina

Petrovsky National Research Centre of Surgery, Moscow, Russia

Author for correspondence.
Email: yu.v.markina@gmail.com

Cand. Sci. (Med.), Senior Researcher, Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Centre of Surgery

Russian Federation, г. Москва, Абрикосовский переулок, д.2

References

  1. Zhang T, Pang C, Xu M, Zhao Q, Hu Z, Jiang X, Guo M. The role of immune system in atherosclerosis: Molecular mechanisms, controversies, and future possibilities. Hum Immunol. 2024, 85(2), 110765. doi: 10.1016/j.humimm.2024.110765.
  2. Hutton M, Frazer M, Lin A, Patel S, Misra A. New Targets in Atherosclerosis: Vascular Smooth Muscle Cell Plasticity and Macrophage Polarity. Clin Ther. 2023, 45(11), 1047-1054. doi: 10.1016/j.clinthera.2023.08.015.
  3. Nikiforov NG, Kirichenko TV, Kubekina MV, Chegodaev YS, Zhuravlev AD, Ilchuk LA, Nikolaeva MA, Arefieva AS, Popov MA, Verkhova SS, Bagheri Ekta M, Orekhov AN. Macrophages derived from LPS-stimulated monocytes from individuals with subclinical atherosclerosis were characterized by increased pro-inflammatory activity. Cytokine. 2023, 172, 156411. doi: 10.1016/j.cyto.2023.156411.
  4. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res. 2017, 120(1), 229-243. doi: 10.1161/CIRCRESAHA.116.308537
  5. Singh M, McEvoy JW, Khan SU, Wood DA, Graham IM, Blumenthal RS, Mishra AK, Michos ED. Comparison of Transatlantic Approaches to Lipid Management: The AHA/ACC/Multisociety Guidelines vs the ESC/EAS Guidelines. Mayo Clin Proc. 2020, 95(5), 998-1014. doi: 10.1016/j.mayocp.2020.01.011.
  6. Pedersen TR. Pleiotropic effects of statins: evidence against benefits beyond LDL-cholesterol lowering. Am J Cardiovasc Drugs. 2010, 10(1), 10-17. doi: 10.2165/1158822-S0-000000000-00000.
  7. Kauerova S, Bartuskova H, Muffova B, Janousek L, Fronek J, Petras M, Poledne R, Kralova Lesna I. Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation. Biomedicines. 2021, 9(2), 211. doi: 10.3390/biomedicines9020211.
  8. Ruleva NY, Radyukhina NV, Zubkova ES, Filatova AY, Aref'eva TI. Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase (Statins) Suppress Differentiation and Reduce LPS/IFNγ-Induced Cytokine Production in Human Monocyte/Macrophage Culture. Bull Exp Biol Med. 2020, 170(2), 236-240. doi: 10.1007/s10517-020-05042-x.
  9. Jinnouchi H, Guo L, Sakamoto A, Torii S, Sato Y, Cornelissen A, Kuntz S, Paek KH, Fernandez R, Fuller D, Gadhoke N, Surve D, Romero M, Kolodgie FD, Virmani R, Finn AV. Diversity of macrophage phenotypes and responses in atherosclerosis. Cell Mol Life Sci. 2020, 77(10), 1919-1932. doi: 10.1007/s00018-019-03371-3.
  10. Lin P, Ji HH, Li YJ, Guo SD. Macrophage Plasticity and Atherosclerosis Therapy. Front Mol Biosci. 2021, 8, 679797. doi: 10.3389/fmolb.2021.679797.
  11. Koushki K, Shahbaz SK, Mashayekhi K, Sadeghi M, Zayeri ZD, Taba MY, Banach M, Al-Rasadi K, Johnston TP, Sahebkar A. Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways. Clin Rev Allergy Immunol. 2021, 60(2), 175-199. doi: 10.1007/s12016-020-08791-9.
  12. Zhang X, Qin Y, Wan X, Liu H, Lv C, Ruan W, He L, Lu L, Guo X. Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities. J Transl Med. 2021, 19(1), 62. doi: 10.1186/s12967-021-02727-3.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) Kirichenko T.V., Yudina I.Y., Lukina M.V., Andrushchishina T.B., Zhivodernikov I.V., Markina Y.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies