Morphological features of atherosclerotic plaque: modeling of atherosclerosis after stenting as a model of premature aging

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Atherosclerosis and the installation of stents can be considered as a model of premature aging of the body. These processes are associated with chronic inflammation, oxidative stress, loss of cellular function, and impaired regeneration, which makes them a convenient model for studying the mechanisms of age-related pathology.

The aim of the study was an immunohistochemical study for the following markers: α-SMA, c-kit, endothelin I on a model of generalized atherosclerosis in experimental animals.

Material and methods. The experiment included 23 male rabbits of the Soviet Chinchilla breed, obtained from a certified nursery and kept in standardized conditions with controlled light, temperature and humidity. The animals were divided into three groups: intact rabbits (n=3), rabbits on a cholesterol diet (n=10) and rabbits on a cholesterol diet with a stent (n=10). Histological and immunohistochemical analysis of tissues was performed using standard techniques, including hematoxylin-eosin staining, detection of proteins α-SMA, endothelin-1 and c-Kit, morphometry using automated image analysis, statistical data processing was performed using StatTech v software.3.1.10.

Results. The level of endothelin-1 increases sharply with atherosclerosis and increases especially strongly after the installation of a stent, which indicates a violation of the inner lining of the vessel and narrowing of the lumen of the arteries. The level of C-kit protein also increases markedly with atherosclerosis, and is even more pronounced after stenting, which indicates the activation of vascular repair processes. At the same time, the amount of α-SMA protein decreases as a signal of the loss of the ability of vascular muscle cells to contract and indicates an increase in inflammatory changes in the vascular wall.

Conclusion. In the course of the study, an experimental model of atherosclerosis and stenting in rabbits was reproduced, which makes it possible to study the molecular and cellular mechanisms of vascular pathology associated with premature aging. Immunohistochemical analysis showed a significant increase in the expression of α-SMA, endothelin-1 and c-Kit in atherosclerotic plaque, especially in the group of animals undergoing stenting, which indicates increased proliferation of smooth muscle cells and endothelial dysfunction. The data obtained confirm that a high-cholesterol diet and the installation of a stent cause not only structural changes in the vascular wall, but also activate inflammatory processes similar to those observed with age-related vascular changes in humans.

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作者简介

Kirill Kozlov

Private educational institution of higher education “St. Petersburg Medical and Social Institute”

编辑信件的主要联系方式.
Email: kozlov_kl@mail.ru
ORCID iD: 0000-0003-3660-5864

Leading Researcher, Doctor of Medical Sciences, Professor

俄罗斯联邦, 195271, Kondratievsky ave., 72, lit. A, St. Petersburg

Alexey Sopromadze

Private educational institution of higher education “St. Petersburg Medical and Social Institute”

Email: sopral@mail.ru
ORCID iD: 0009-0001-8478-947X

Student

俄罗斯联邦, 195271, Kondratievsky ave., 72, lit. A, St. Petersburg

Dmitry Medvedev

Private educational institution of higher education “St. Petersburg Medical and Social Institute”

Email: mds@dsmedvedev.ru
ORCID iD: 0000-0001-7401-258X

Doctor of Medical Science, Professor, Leading researcher, Departments of Medical and Social rehabilitation and Occupational Therapy

俄罗斯联邦, 195271, Kondratievsky ave., 72, lit. A, St. Petersburg

Andrey Borodulin

Saint Petersburg State University

Email: avborodulin@list.ru
ORCID iD: 0000-0002-4944-2593

Associate Professor, Department of General Surgery, Candidate of Medical Sciences

俄罗斯联邦, 199034, Universitetskaya amb. 7–9, St. Petersburg

Victoria Polyakova

Private educational institution of higher education “St. Petersburg Medical and Social Institute”

Email: vopol@yandex.ru
ORCID iD: 0000-0001-8682-9909

Professor, Doctor of Biological Sciences, Professor, Professor of the Russian Academy of Sciences

俄罗斯联邦, 195271, Kondratievsky ave., 72, lit. A, St. Petersburg

参考

  1. Abdalwahab A., Farag M., Brilakis E.S., Galassi A.R., Egred M. Management of coronary artery perforation. Cardiovascular Revascularization Medicine. 2021; 26: 55–60. doi: 10.1016/j.carrev.2020.11.013.
  2. Alfonso F., Coughlan J.J., Giacoppo D., Kastrati A., Byrne R.A. Management of in-stent restenosis. EuroIntervention. 2022; 18 (2): 103. doi: 10.4244/EIJ-D-21-01034.
  3. Cassese S., Byrne R.A., Tada T., Pinieck S., Joner M., Ibrahim T., King L.A. et al. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart. 2014; 100 (2): 153–9. doi: 10.1136/heartjnl-2013-304933
  4. Hu W., Jiang J. Hypersensitivity and in-stent restenosis in coronary stent materials. Frontiers in bioengineering and biotechnology. 2022; 10: 1003322. doi: 10.3389/fbioe.2022.1003322.
  5. Chen Z., Matsumura M., Mintz G.S., Noguchi M., Fujimura T., Usui E., Seike F. et al. Prevalence and impact of neoatherosclerosis on clinical outcomes after percutaneous treatment of second-generation drug-eluting stent restenosis. Circulation: Cardiovascular Interventions. 2022: 15 (9): 011693. doi: 10.1161/CIRCINTERVENTIONS.121.011693.
  6. Clare J., Ganly J., Bursill C.A., Sumer H., Kingshott P., de Haan J.B. The mechanisms of restenosis and relevance to next generation stent. Biomolecules. 2022; 12 (3): 430. doi: 10.3390/biom12030430.
  7. Hubert A., Seitz A., Pereyra V.M., Bekeredjian R., Sechtem U., Ong P. Coronary artery spasm: the interplay between endothelial dysfunction and vascular smooth muscle cell hyperreactivity. European Cardiology Review. 2020; 15: 15. doi: 10.15420/ecr.2019.20.
  8. Pal N., Din J., O'Kane P. Contemporary management of stent failure: part one O’Kane. Interventional Cardiology Review. 2019; 14 (1): 10–6. doi: 10.15420/icr.2018.39.1.
  9. Labarrere C.A., Dabiri A. E., Kassab G. S. Thrombogenic and inflammatory reactions to biomaterials in medical devices. Frontiers in Bioengineering and biotechnology. 2020; 8: 123. doi: 10.3389/fbioe.2020.00123.
  10. Madhavan M.V., Kirtane A.J., Redfors B., Généreux P., Ben-Yehuda O., Palmerini T., Benedetto U. et al. Stent-related adverse events > 1 year after percutaneous coronary intervention. J. of the American College of Cardiology. 2020; 75 (6): 590–604. doi: 10.1016/j.jacc.2019.11.058.
  11. Condello F., Spaccarotella C., Sorrentino S., Indolfi C., Stefanini G.G., Polimeni A., Condello F. Stent thrombosis and restenosis with contemporary drug-eluting stents: predictors and current evidence. J. of clinical medicine. 2023; 12 (3): 1238. doi: 10.3390/jcm12031238.
  12. Чаулин А.М., Григорьева Ю.В., Суворова Г.Н., Дупляков Д.В. Способы моделирования атеросклероза у кроликов. Современные проблемы науки и образования. 2020; 5: 141. doi: 10.17513/spno.30101 [Chaulin A.M., Grigorieva Yu.V., Suvorova G.N., Duplyakov D.V. Methods of modeling atherosclerosis in rabbits. Modern problems of science and education. 2020; 5: 141. doi: 10.17513/spno.30101 (in Russian)]
  13. Чаулин А.М., Григорьева Ю.В., Суворова Г.Н., Дупляков Д.В. Экспериментальные модели атеросклероза на кроликах. Морфологические ведомости. 2020; 28 (4): 78–87 [Chaulin A.M., Grigorieva Yu.V., Suvorova G.N., Duplyakov D.V. Experimental models of atherosclerosis in rabbits. Morphological bulletin. 2020; 28 (4): 78–87 (in Russian)]
  14. Suryawan I.G.R., Luke K., Agustianto R.F., Mulia EP.B. Coronary stent infection: a systematic review. Coronary Artery Disease. 2022; 33 (4): 318–26. doi: 10.1097/MCA.0000000000001098.
  15. Cornelissen A., Vogt F.J. The effects of stenting on coronary endothelium from a molecular biological view: Time for improvement? J. of cellular and molecular medicine. 2019; 23 (1): 39–46. doi: 10.1111/jcmm.13936.
  16. Kawasaki Y., Imaizumi T., Matsuura H., Ohara S., Takano K., Suyama K., Hashimoto K. et al. Renal expression of alpha-smooth muscle actin and c-Met in children with Henoch-Schonlein purpura nephritis. Pediatr Nephrol. 2008; 23 (6): 913–9. doi: 10.1007/s00467- 008-0749-6.
  17. Nakatani T., Honda E., Hayakawa S., Sato M., Satoh K., Kudo M., Munakata H. Effects of decorin on the expression of alpha-smooth muscle actin in a human myofibroblast cell line. Mol Cell Biochem. 2008; 308 (1–2): 201–7. doi: 10.1007/s11010-007-9629-9.
  18. Mammana C., Russo G., Tamburino C., Galassi A.R., Nicosia A., Grassi R., Monaco A. et al. Variazione di endotelina-1 nel circolo coronarico durante angioplastica con impianto di stent [Endothelin-1 variation in the coronary circulation during angioplasty with a stent implant]. Cardiologia. 1998; 43 (10): 1083–8. PMID: 9922573.
  19. Сваровская А.В., Кужелева Е.А., Огуркова О.Н., Гарганеева А.А. Значимость абдоминального ожирения и маркера эндотелиальной дисфункции у пациентов, перенесших плановое стентирование коронарных артерий. Сибирский журнал клинической и экспериментальной медицины. 2021; 36 (3): 97–103. doi: 10.29001/2073-8552-2021-36-3-97-103 [Swarovskaya A.V., Kuzheleva E.A., Ogurkova O.N., Garganeeva A.A. The significance of abdominal obesity and a marker of endothelial dysfunction in patients undergoing elective coronary artery stenting. Siberian J. of Clinical and Experimental Medicine. 2021; 36 (3): 97–103. doi: 10.29001/2073-8552-2021-36-3-97-103 (in Russian)]
  20. Ouerd S., Idris-Khodja N., Trindade M., Ferreira N.S., Berillo O., Coelho S.C., Neves M.F. et al. Endotheliumrestricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1. Cardiovasc Res. 2021: 117 (4): 1144–153. doi: 10.1093/cvr/cvaa168.
  21. Zhang C., Tian J., Jiang L., Xu L., Liu J., Zhao X., Feng X. et al. Prognostic value of plasma big endothelin-1 level among patients with three-vessel disease: A cohort study. J. Atheroscler. Thromb. 2019; 26 (11): 959–69. doi: 10.5551/jat.47324.
  22. Li M.W., Mian M.O., Barhoumi T., Rehman A., Mann K., Paradis P., Schiffrin EL. Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice. Arterioscler. Thromb. Vasc. Biol. 2013; 33 (10): 2306–15. doi: 10.1161/ATVBAHA.113.302028.
  23. Davenport A.P., Hyndman K.A., Dhaun N., Southan C., Kohan D.E., Pollock J.S., Pollock D.M. et al. Endothelin. Pharmacol. Rev. 2016; 68 (2): 357–418. doi: 10.1124/pr.115.011833.
  24. Дергилев К.В., Цоколаева З.И., Белоглазова И.Б., Ратнер Е.И., Молокотина Ю.Д., Парфенова Е.В. Характеристика ангиогенных свойств ckit+-клеток миокарда. Гены & Клетки. 2018; XIII (3): 82–8. doi: 10.23868/201811038. [Dergilev K.V., Tsokolaeva Z.I., Beloglazova I.B., Ratner E.I., Molokotina Yu.D., Parfenova E.V. Characteristics of angiogenic properties of ckit+cells of the myocardium. Genes & Cells. 2018; XIII (3): 82–8. doi: 10.23868/201811038 (in Russian)]
  25. Song L., Zigmond Z.M., Martinez L., Lassance-Soares R.M., Macias A.E., Velazquez O.C., Liu Z.J. et al. Vazquez-Padron RI. c-Kit suppresses atherosclerosis in hyperlipidemic mice. Am. J. Physiol Heart Circ Physiol. 2019; 317 (4): 867–76. doi: 10.1152/ajpheart.00062.2019.
  26. Jain M., Frobert A., Valentin J., Cook S., Giraud M.N. The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury. J. Vis Exp. 2017; 128: 55295. doi: 10.3791/55295.
  27. Fan J., Unoki H., Iwasa S., Watanabe T. Role of endothelin-1 in atherosclerosis. Ann N. Y. Acad Sci. 2000; 902: 84–93. doi: 10.1111/j.1749-6632.
  28. Bousette N., Giaid A. Endothelin-1 in atherosclerosis and other vasculopathies. Can J. Physiol Pharmacol. 2003; 81 (6): 578–87. doi: 10.1139/y03-010.
  29. Wang L., Cheng C.K., Yi M., Lui K.O., Huang Y. Targeting endothelial dysfunction and inflammation. J. Mol. Cell. Cardiol. 2022; 168: 58–67. doi: 10.1016/j.yjmcc.2022.04.011.
  30. Weiss D., Sorescu D., Taylor W.R. Angiotensin II and atherosclerosis. Am. J. Cardiol. 2001; 87 (8A): 25–32. doi: 10.1016/s0002-9149(01)01539-9.
  31. Wang L., Cheng C.K., Yi M., Lui K.O., Huang Y. Targeting endothelial dysfunction and inflammation. J. Mol. Cell. Cardiol. 2022; 168: 58–67. doi: 10.1016/j.yjmcc.2022.04.011.
  32. Zigmond Z.M., Song L., Martinez L., Lassance-Soares R.M., Velazquez O.C., Vazquez-Padron R.I. c-Kit expression in smooth muscle cells reduces atherosclerosis burden in hyperlipidemic mice. Atherosclerosis. 2021; 324: 133–40. doi: 10.1016/j.atherosclerosis.2021.03.004.

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2. Fig. 1. Carotid Artery Access Stage

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3. Fig. 2. The stage of allocation of the neurovascular bundle in the medial part of the neck

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4. Fig. 3. The stage of carotid artery mobilization

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