Атеросклероз и воспаление – путь от патогенеза к терапии: обзор современного состояния проблемы (часть 1)

Атеросклероз и ассоциированные с ним болезни системы кровообращения являются актуальной проблемой общественного здравоохранения, а также активно развивающимся направлением исследований как в фундаментальной, так и клинической медицине. Несмотря на многолетнюю историю изучения заболевания, до сих пор многие аспекты этиологии и патогенеза атеросклероза остаются неясными.
Традиционно патогенез атеросклероза рассматривают с позиции очагового накопления отдельных фракций липопротеинов в сосудистой стенке артерий. Однако в атерогенезе активное участие принимают факторы как врожденного, так и адаптивного иммунитета. Клетки и медиаторы иммунной системы вступают в сложное взаимодействие с клеточным и внеклеточным компонентами всех слоев сосудистой стенки. Вследствие этого большинство исследователей пришли к консенсусу о ключевой роли воспаления в инициации, прогрессировании, а также дестабилизации атеросклеротической бляшки.
Таким образом, атерогенез можно рассматривать не только как дисметаболический, но и как иммуновоспалительный процесс. Целью настоящей лекции является обобщение новейших данных о роли воспаления на разных этапах атеросклеротического континуума.

1. Погосова Н.В., Бойцов С.А. Профилактическая кардиология 2024: состояние проблемы и перспективы развития. Кардиология. 2024;64(1):4–13. DOI: 10.18087/cardio.2024.1.n2636.

2. World Health Organization. Political declaration of the high-level meeting of the General Assembly on the prevention and control of non-communicable diseases. High-level Plenary Meeting of the General Assembly. Geneva, Switzerland, 2011.

3. Bagheri Kholenjani F., Shahidi S., Vaseghi G., Ashoorion V., Sarrafzadegan N., Siavash M. et al. First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults. J. Res. Med. Sci. 2024;29:18. DOI: 10.4103/jrms.jrms_318_23.

4. Elsadek R., Bassi R., Ismail Z., Oyetoran A., Perbtani Y., Brar T. et al. The association between adverse cardiovascular outcomes in celiac disease and the role of inflammation: Retrospective analysis using the national inpatient sample. Curr. Probl. Cardiol. 2024;49(8):102612. DOI: 10.1016/j.cpcardiol.2024.102612.

5. Бойцов С.А., Погосова Н.В., Аншелес А.А., Бадтиева В.А., Балахонова Т.В., Барбараш О.Л. и др. Кардиоваскулярная профилактика 2022. Российские национальные рекомендации. Российский кардиологический журнал. 2023;28(5):5452. DOI: 10.15829/1560-4071-2023-5452.

6. Pogosova N., Bosch J., Bhatt D.L., Fox K.A.A., Connolly S.J., Alings M. et al. Rivaroxaban 2.5 mg twice daily plus aspirin reduces venous thromboembolism in patients with chronic atherosclerosis. Circulation. 2022;145(25):1875–1877. DOI: 10.1161/CIRCULATIONAHA.122.059405.

7. Fan J., Watanabe T. Atherosclerosis: known and unknown. Pathol. Int. 2022;72(3):151–160. DOI: 10.1111/pin.13202.

8. Cameron J.N., Mehta O.H., Michail M., Chan J., Nicholls S.J., Bennett M. et al. Exploring the relationship between biomechanical stresses and coronary atherosclerosis. Atherosclerosis. 2020;302:43–51. DOI: 10.1016/j.atherosclerosis.2020.04.011.

9. Demos C., Tamargo I., Jo H. Biomechanical regulation of endothelial function in atherosclerosis. In: Biomechanics of Coronary Atherosclerotic. Plaque. 2021:3–47. DOI: 10.1016/B978-0-12-817195-0.00001-9.

10. Погосова Н.В., Оганов Р.Г., Бойцов С.А., Аушева А.К., Соколова О.Ю., Курсаков А.А. и др. Анализ ключевых показателей вторичной профилактики у пациентов с ишемической болезнью сердца в России и Европе по результатам российской части международного многоцентрового исследования EUROASPIRE V. Кардиоваскулярная терапия и профилактика. 2020;19(6):2739. DOI: 10.15829/1728-8800-2020-2739.

11. Погосова Н.В., Оганов Р.Г., Бойцов С.А., Аушева А.К., Соколова О.Ю., Курсаков А.А. и др. Эффективность первичной профилактики заболеваний, обусловленных атеросклерозом, у пациентов с высоким сердечно-сосудистым риском в России и других странах Европы (часть 1). Кардиология. 2017;57(1S):333–344. DOI: 10.18087/cardio.2411.

12. Avagimyan A., Kakturskiy L., Heshmat-Ghahdarijani K., Pogosova N., Sarrafzadegan N. Anthracycline associated disturbances of cardiovascular homeostasis. Curr. Probl. Cardiol. 2022;47(5):100909. DOI: 10.1016/j.cpcardiol.2021.100909.

13. Avagimyan A., Pogosova N., Kakturskiy L., Sheibani M., Urazova O., Trofimenko A. et al. HIV-Related Atherosclerosis: State-of-the-Art-Review. Curr. Probl. Cardiol. 2023;48(9):101783. DOI: 10.1016/j.cpcardiol.2023.101783.

14. Авагимян А.А., Мкртчян Л.Г., Навасардян Г.А., Геворкян А.А., Ананян Э.А., Пашинян Н.Э. и др. Роль Helicobacter pylori в механизмах кардио- и вазотоксичности. Российский кардиологический журнал. 2019;(12):169–174. DOI: 10.15829/1560-4071-2019-12-169-174.

15. Avagimyan A., Manukyan I., Navasardyan G., Chelidze K., Risovaniy S. The atherogenic impact of oral cavity dysbiosis (review). Georgian Med. News. 2020;(304-305):69–74.

16. Гордеев А.В., Олюнин Ю.А., Галушко Е.А., Зоткин Е.Г., Лила А.М. Ревматоидный артрит и сердечно-сосудистые заболевания: близкие родственники или друзья? Современная ревматология. 2023;17(2):16–22. DOI: 10.14412/1996-7012-2023-2-16-22.

17. Ridker P.M., Bhatt D.L., Pradhan A.D., Glynn R.J., MacFadyen J.G., Nissen S.E. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401(10384):1293–1301. DOI: 10.1016/S0140-6736(23)00215-5.

18. Nidorf S.M., Ben-Chetrit E., Ridker P.M. Low-dose colchicine for atherosclerosis: long-term safety. Eur. Heart J. 2024;45(18):1596–1601. DOI: 10.1093/eurheartj/ehae208.

19. Surma S., Sahebkar A., Banach M. Correction to: whether and why do we need a vaccine against atherosclerosis? Can we expect it anytime soon? Curr. Atheroscler. Rep. 2024;26(3):73. DOI: 10.1007/s11883-024-01189-4.

20. Poznyak A., Bezsonov E., Popkova T., Starodubova A.V., Orekhov A.N. Vaccination against atherosclerosis: is it real? Int. J. Mol. Sci. 2022;23(5):2417. DOI: 10.3390/ijms23052417.

21. Naseem S., Sun L., Qiu J. Stress granules in atherosclerosis: Insights and therapeutic opportunities. Curr. Probl. Cardiol. 2024;49(10):102760. DOI: 10.1016/j.cpcardiol.2024.102760.

22. Zeng G.G., Zhou J., Jiang W. L., Yu J., Nie G.Y., Li J. et al. A potential role of nfil3 in atherosclerosis. Curr. Probl. Cardiol. 2024;49(1 Pt B):102096. DOI: 10.1016/j.cpcardiol.2023.102096.

23. Pyrpyris N., Dimitriadis K., Beneki E., Iliakis P., Soulaidopoulos S., Tsioufis P. et al. LOX-1 receptor: a diagnostic tool and therapeutic target in atherogenesis. Curr. Probl. Cardiol. 2024;49(1 Pt C):102117. DOI: 10.1016/j.cpcardiol.2023.102117.

24. Alkhalil M. Mechanistic insights to target atherosclerosis residual risk. Curr. Probl. Cardiol. 2021;46(3):100432. DOI: 10.1016/j.cpcardiol.2019.06.004.

25. Chen Y., Wang X., Mai J., Zhao X., Liang Y., Gu M. et al. C-reactive protein promotes vascular endothelial dysfunction partly via activating adipose tissue inflammation in hyperlipidemic rabbits. Int. J. Cardiol. 2013;168(3):2397–2403. DOI: 10.1016/j.ijcard.2013.01.158.

26. Hemling P., Zibrova D., Strutz J., Sohrabi Y., Desoye G., Schulten H. et al. Hyperglycemia-induced endothelial dysfunction is alleviated by thioredoxin mimetic peptides through the restoration of VEGFR-2-induced responses and improved cell survival. Int. J. Cardiol. 2020;308:73–81. DOI: 10.1016/j.ijcard.2019.12.065.

27. Joshi M.S., Tong L., Cook A.C., Schanbacher B.L., Huang H., Han B. et al. Increased myocardial prevalence of C-reactive protein in human coronary heart disease: direct effects on microvessel density and endothelial cell survival. Cardiovasc. Pathol. 2012;21(5):428–435. DOI: 10.1016/j.carpath.2011.12.003.

28. Mungmunpuntipantip R., Wiwanitkit V. Cardiac inflammation associated with COVID-19 mRNA vaccination and previous myocarditis. Minerva Cardiol. Angiol. 2024;72(2):214–215. DOI: 10.23736/S2724-5683.23.06346-9.

29. Haeri S.M.J., Dashti G.R., Mardani M., Rashidi B., Nikgoftar Fathi A., Haeri N. Effect of vitamin e on apoptosis of the endothelial cells of the carotid arteries in hypercholesterolemic male rabbits. Arya Atheroscler. 2023;19(3):10–17. DOI: 10.22122/arya.2022.39175.2824.

30. Heshmat-Ghahdarijani K., Jangjoo S., Amirpour A., Najafian J., Khosravi A., Heidarpour M. et al. Endothelial dysfunction in patients with lone atrial fibrillation. ARYA. Atheroscler. 2020;16(6):278–283. DOI: 10.22122/arya.v16i6.2095.

31. Учасова Е.Г., Груздева О.В., Дылева Ю.А., Акбашева О.Е. Эпикардиальная жировая ткань: патофизиология и роль в развитии сердечно-сосудистых заболеваний. Бюллетень сибирской медицины. 2018;17(4):254–263. DOI: 10.20538/1682-0363-2018-4-254-263.

32. Avagimyan A., Popov S., Shalnova S. The pathophysiological basis of diabetic cardiomyopathy development. Curr. Probl. Cardiol. 2022;47(9):101156. DOI: 10.1016/j.cpcardiol.2022.101156.

33. Avagimyan A., Fogacci F., Pogosova N., Kakrurskiy L., Kogan E., Urazova O. et al. Diabetic cardiomyopathy: 2023 update by the international multidisciplinary board of experts. Curr. Probl. Cardiol. 2024;49(1 Pt A):102052. DOI: 10.1016/j.cpcardiol.2023.102052.

34. Aznauryan A.V., Navasardyan G.A., Avagimyan A.A. Perivascular adipose tissue – orchestrator of cardiovascular disturbances sequel. The New Armenian Medical Journal. 2022;16(4):107–114. DOI: 10.56936/18290825-2022.16.4-107.

35. Tinajero M.G., Gotlieb A.I. Recent developments in vascular adventitial pathobiology: the dynamic adventitia as a complex regulator of vascular disease. Am. J. Pathol. 2020;190(3):520–534. DOI: 10.1016/j.ajpath.2019.10.021.

36. Ardiana M., Pikir B., Santoso A., Suryawan I., Hermawan H., Rachmi D. et al. Effect of black cumin ethanolic extract administration to superoxide dismutase and malondialdehyde in inhibiting endothelial dysfunction in cigarette exposed rats. ARYA Atherosclerosis. 2022;18(5):1–9. DOI: 10.48305/arya.2022.11756.2387.

37. Ma Y., Li Y., Yang Y., Li P. The Microenvironment that regulates vascular wall stem/progenitor cells in vascular injury and repair. Biomed. Res. Int. 2022;2022:9377965. DOI: 10.1155/2022/9377965.

38. Karpathiou G., Dumollard J. M., Camy F., Sramek V., Dridi M., Picot T. et al. Senescence, immune microenvironment, and vascularization in cardiac myxomas. Cardiovasc. Pathol. 2021;52:107335. DOI: 10.1016/j.carpath.2021.107335.

39. Hall S.A., Lesniewski L.A. Targeting vascular senescence in cardiovascular disease with aging. J. Cardiovasc. Aging. 2024;4(2):16. DOI: 10.20517/jca.2023.45.

40. Kishimoto Y., Kondo K., Momiyama Y. The protective role of Sestrin2 in atherosclerotic and cardiac diseases. Int. J. Mol. Sci. 2021;22(3):1200. DOI: 10.3390/ijms22031200.

41. Ионов А.Ю., Кузнецова Е.А., Киндалёва О.Г., Крючкова И.В., Поплавская Э.Э., Авагимян А.А. Клиническое значение эндокринных нарушений в развитии синдрома раннего сосудистого старения у мужчин с абдоминальным ожирением и сопутствующей артериальной гипертензией: обсервационное когортное исследование. Кубанский научный медицинский вестник. 2024;31(1):74–87. DOI: 1 0.25207/1608-6228-2024-31-1-74-87.

42. Borén J., Chapman M.J., Krauss R.M., Packard C.J., Bentzon J.F., Binder C.J. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2020;41(24):2313–2330. DOI: 10.1093/eurheartj/ehz962.

43. Fatahian A. Nebivolol for improving endothelial dysfunction in cardiac syndrome-x; Is it ready for clinical use? ARYA Atheroscler. 2019;15(6):292–293. DOI: 10.22122/arya.v15i6.1971.

44. Tanyanskiy D.A., Pigarevskii P.V., Maltseva S.V., Denisenko A.D. Immunohistochemical analysis of adiponectin in atherosclerotic lesions of human aorta. ARYA Atheroscler. 2019;15(4):179–184. DOI: 10.22122/arya.v15i4.1873.

45. Esfahani M., Saidijam M., Najafi R., Goodarzi M. T., Movahedian A. The effect of salusin-β on expression of pro- and anti-inflammatory cytokines in human umbilical vein endothelial cells (HUVECs). ARYA Atheroscler. 2018;14(1):1–10. DOI: 10.22122/arya.v14i1.1602.

46. He W., Holtkamp S., Hergenhan S. M., Kraus K., de Juan A., Weber J. et al. Circadian expression of migratory factors establishes lineage-specific signatures that guide the homing of leukocyte subsets to tissues. Immunity. 2018;49(6):1175–1190.e7. DOI: 10.1016/j.immuni.2018.10.007.

47. Lin J., Kakkar V., Lu X. Impact of MCP-1 in atherosclerosis. Curr. Pharm. Des. 2014;20(28):4580–4588. DOI: 10.2174/1381612820666140522115801.

48. Attiq A., Afzal S., Ahmad W., Kandeel M. Hegemony of inflammation in atherosclerosis and coronary artery disease. Eur. J. Pharmacol. 2024;966:176338. DOI: 10.1016/j.ejphar.2024.176338.

49. Дутова С.В., Саранчина Ю.В., Карпова М.Р., Килина О.Ю., Польша Н.Г., Кулакова Т.С. и др. Цитокины и атеросклероз – новые направления исследований. Бюллетень сибирской медицины. 2018;17(4):199–208. DOI: 10.20538/1682-0363-2018-4-199-207.

50. Лобанова Н.Ю., Чичерина Е.Н. Нетрадиционные факторы риска и их значение в оценке сердечнососудистого риска у бессимптомных пациентов. Бюллетень сибирской медицины. 2020;19(2):182–188. DOI: 10.20538/1682-0363-2020-2-182-188.

51. Ryzhkova A.I., Karagodin V.P., Sukhorukov V.N., Sazonova M.A., Orekhov A.N. Desialated low density lipoproteins in human blood. Klin. Med. (Mosk.). 2017;95(3):216–221. DOI: 10.18821/0023-2149-2017-95-3-216-221.

52. Romeo F.J., Del Buono M.G., Aguilar-Gallardo J.S., Lorente-Ros M., Damonte J.I., Chiabrando J.G. et al. Cardiac remodeling with SGLT2 inhibitors in heart failure with reduced ejection fraction. Minerva Cardiol. Angiol. 2024;72(1):95–97. DOI: 10.23736/S2724-5683.22.06207-X.

53. Huang Q., Gan Y., Yu Z., Wu H., Zhong Z. Endothelial to mesenchymal transition: an insight in atherosclerosis. Front. Cardiovasc. Med. 2021;8:734550. DOI: 10.3389/fcvm.2021.734550.

54. Gonzalez A.L., Dungan M.M., Smart C.D., Madhur M.S., Doran A.C. Inflammation resolution in the cardiovascular system: arterial hypertension, atherosclerosis, and ischemic heart disease. Antioxid. Redox Signal. 2024;40(4-6):292–316. DOI: 10.1089/ars.2023.0284.

55. Авагимян А.А., Чернова А.А., Азнаурян А.З. Роль вирусной инфекции в механизмах инициирования атерогенеза и дестабилизации атеромы. Кардиология в Беларуси. 2019;11(6):947–953.

56. Zhang X., Kang Z., Yin D., Gao J. Role of neutrophils in different stages of atherosclerosis. Innate Immun. 2023;29(6):97–109. DOI: 10.1177/17534259231189195.

57. Döring Y., Drechsler M., Soehnlein O., Weber C. Neutrophils in atherosclerosis: from mice to man. Arterioscler. Thromb. Vasc. Biol. 2015;35(2):288–295. DOI: 10.1161/ATVBAHA.114.303564.

58. Avagimyan A. Hyperhomocysteinemia as a Link of chemotherapy-related endothelium impairment. Curr. Probl. Cardiol. 2022;47(10):100932. DOI: 10.1016/j.cpcardiol.2021.100932.

59. Apostolakis S., Spandidos D. Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway. Acta Pharmacol. Sin. 2013;34(10):1251–1256. DOI: 10.1038/aps.2013.92.

60. Ng C.T., Fong L.Y., Abdullah M.N.H. Interferon-gamma (IFN-γ): Reviewing its mechanisms and signaling pathways on the regulation of endothelial barrier function. Cytokine. 2023;166:156208. DOI: 10.1016/j.cyto.2023.156208.

61. Tran D.T., Batchu S.N., Advani A. Interferons and interferon-related pathways in heart disease. Front. Cardiovasc. Med. 2024;11:1357343. DOI: 10.3389/fcvm.2024.1357343.

62. Owens G.K., Kumar M.S., Wamhoff B.R. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 2004;84(3):767–801. DOI: 10.1152/physrev.00041.2003.

63. Li F., Peng J., Lu Y., Zhou M., Liang J., Le C. et al. Blockade of CXCR4 promotes macrophage autophagy through the PI3K/AKT/mTOR pathway to alleviate coronary heart disease. Int. J. Cardiol. 2023;392:131303. DOI: 10.1016/j.ijcard.2023.131303.

64. Ragino Y.I., Volkov A.M., Chernyavskyi A.M. Stages of atherosclerotic plaque development and unstable plaque types: pathophysiologic and histologic characteristics. Russian Journal of Cardiology. 2013;103(5):88–95. DOI: 10.15829/1560-4071-2013-5-88-95.

65. Wu J., He S., Song Z., Chen S., Lin X., Sun H. et al. Macrophage polarization states in atherosclerosis. Front. Immunol. 2023;14:1185587. DOI: 10.3389/fimmu.2023.1185587.

66. Choi H., Dey A.K., Priyamvara A., Aksentijevich M., Bandyopadhyay D., Dey D. et al. Role of periodontal infection, inflammation and immunity in atherosclerosis. Curr. Probl. Cardiol. 2021;46(3):100638. DOI: 10.1016/j.cpcardiol.2020.100638.

67. Gusev E., Sarapultsev A. Atherosclerosis and inflammation: insights from the theory of general pathological processes. Int. J. Mol. Sci. 2023;24(9):7910. DOI: 10.3390/ijms24097910.

68. Fleg J.L., Stone G.W., Fayad Z.A., Granada J.F., Hatsukami T.S., Kolodgie F.D. et al. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc. Imaging. 2012;5(9):941–955. DOI: 10.1016/j.jcmg.2012.07.007.

69. Blagov A.V., Markin A.M., Bogatyreva A.I., Tolstik T.V., Sukhorukov V.N., Orekhov A.N. The role of macrophages in the pathogenesis of atherosclerosis. Cells. 2023;12(4):522. DOI: 10.3390/cells12040522.

70. Susser L.I., Rayner K.J. Through the layers: how macrophages drive atherosclerosis across the vessel wall. J. Clin. Invest. 2022;132(9):e157011. DOI: 10.1172/JCI157011.

71. Farahi L., Sinha S.K., Lusis A.J. Roles of macrophages in atherogenesis. Front. Pharmacol. 2021;12:785220. DOI: 10.3389/fphar.2021.785220.

72. Checkouri E., Blanchard V., Meilhac O. Macrophages in atherosclerosis, first or second row players? Biomedicines. 2021;9(9):1214. DOI: 10.3390/biomedicines9091214.

73. Wieland E.B., Kempen L.J., Donners M.M., Biessen E.A., Goossens P. Macrophage heterogeneity in atherosclerosis: A matter of context. Eur. J. Immunol. 2024;54(1):e2350464. DOI: 10.1002/eji.202350464.

74. Weber C., Habenicht A.J.R., von Hundelshausen P. Novel mechanisms and therapeutic targets in atherosclerosis: inflammation and beyond. Eur. Heart J. 2023;44(29):2672–2681. DOI: 10.1093/eurheartj/ehad304.

75. Brasier A.R. The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc. Res. 2010;86(2):211–218. DOI: 10.1093/cvr/cvq076.

76. Florance I., Ramasubbu S. Current understanding on the role of lipids in macrophages and associated diseases. Int. J. Mol. Sci. 2022;24(1):589. DOI: 10.3390/ijms24010589.

77. Moore K.J., Sheedy F.J., Fisher E.A. Macrophages in atherosclerosis: a dynamic balance. Nat. Rev. Immunol. 2013;13(10):709–721. DOI: 10.1038/nri3520.

78. Hou P., Fang J., Liu Z., Shi Y., Agostini M., Bernassola F. et al. Macrophage polarization and metabolism in atherosclerosis. Cell Death Dis. 2023;14(10):691. DOI: 10.1038/s41419-023-06206-z.

79. Barrett T.J. Macrophages in atherosclerosis regression. Arterioscler. Thromb. Vasc. Biol. 2020;40(1):20–33. DOI: 10.1161/ATVBAHA.119.312802.

80. De Meyer G.R.Y., Zurek M., Puylaert P., Martinet W. Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets. Nat. Rev. Cardiol. 2024;21(5):312–325. DOI: 10.1038/s41569-023-00957-0.

81. Theofilis P., Oikonomou E., Tsioufis K., Tousoulis D. The role of macrophages in atherosclerosis: pathophysiologic mechanisms and treatment considerations. Int. J. Mol. Sci. 2023;24(11):9568. DOI: 10.3390/ijms24119568.

82. Fang F., Xiao C., Li C., Liu X., Li S. Tuning macrophages for atherosclerosis treatment. Regen Biomater. 2022;10:rbac103. DOI: 10.1093/rb/rbac103.

83. Varghese T.P., Chand S., Varghese N.M., Singh R., Yadav S.K. Interplay of inflammatory biomarkers in heart disease patients with depressive symptoms: An update. Curr. Probl. Cardiol. 2024;49(3):102352. DOI: 10.1016/j.cpcardiol.2023.102352.

84. Alsereidi F.R., Khashim Z., Marzook H., Gupta A., AlRawi A.M., Ramadan M.M. et al. Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement. Curr. Probl. Cardiol. 2024;49(5):102524. DOI: 10.1016/j.cpcardiol.2024.102524.

85. Avagimyan A., Gvianishvili T., Gogiashvili L., Kakturskiy L., Sarrafzadegan N., Aznauryan A. Chemotherapy, hypothyroidism and oral dysbiosis as a novel risk factor of cardiovascular pathology development. Curr. Probl. Cardiol. 2023;48(3):101051. DOI: 10.1016/j.cpcardiol.2021.101051.

86. Xu X., Song Z., Mao B., Xu G. Apolipoprotein a1-related proteins and reverse cholesterol transport in antiatherosclerosis therapy: recent progress and future perspectives. Cardiovasc. Ther. 2022;2022:4610834. DOI: 10.1155/2022/4610834.

87. Xie Y., Chen H., Qu P., Qiao X., Guo L., Liu L. Novel insight on the role of Macrophages in atherosclerosis: Focus on polarization, apoptosis and efferocytosis. Int. Immunopharmacol. 2022;113(Pt A):109260. DOI: 10.1016/j.intimp.2022.109260.

88. Coniglio S., Shumskaya M., Vassiliou E. Unsaturated fatty acids and their immunomodulatory properties. Biology (Basel). 2023;12(2):279. DOI: 10.3390/biology12020279.

89. Videla L.A., Valenzuela R., Del Campo A., Zúñiga-Hernández J. Omega-3 lipid mediators: modulation of the M1/M2 macrophage phenotype and its protective role in chronic liver diseases. Int. J .Mol. Sci. 2023;24(21):15528. DOI: 10.3390/ijms242115528.

90. Truthe S., Klassert T.E., Schmelz S., Jonigk D., Blankenfeldt W., Slevogt H. Role of lectin-like oxidized low-density lipoprotein receptor-1 in inflammation and pathogen-associated interactions. J. Innate Immun. 2024;16(1):105–132. DOI: 10.1159/000535793.

91. Noor R., Shuaib U., Wang C.X., Todd K., Ghani U., Schwindt B. et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis. 2007;192(1):92–99. DOI: 10.1016/j.atherosclerosis.2006.06.023.

92. Tso C., Martinic G., Fan W.H., Rogers C., Rye K.A., Barter P.J. High-density lipoproteins enhance progenitor-mediated endothelium repair in mice. Arterioscler. Thromb. Vasc. Biol. 2006;26(5):1144–1149. DOI: 10.1161/01.ATV.0000216600.37436.cf.

93. Wojtasińska A., Frąk W., Lisińska W., Sapeda N., Młynarska E., Rysz J. et al. Novel insights into the molecular mechanisms of atherosclerosis. Int. J. Mol. Sci. 2023;24(17):13434. DOI: 10.3390/ijms241713434.

94. Van Gils J.M., Ramkhelawon B., Fernandes L., Stewart M.C., Guo L., Seibert T. et al. Endothelial expression of guidance cues in vessel wall homeostasis dysregulation under proatherosclerotic conditions. Arterioscler. Thromb. Vasc. Biol. 2013;33(5):911–919. DOI: 10.1161/ATVBAHA.112.301155.

95. Vreeken D., Zhang H., van Zonneveld A.J., van Gils J.M. Ephs and ephrins in adult endothelial biology. Int. J. Mol. Sci. 2020;21(16):5623. DOI: 10.3390/ijms21165623.

96. Kang H., Li X., Xiong K., Song Z., Tian J., Wen Y. et al. The entry and egress of monocytes in atherosclerosis: a biochemical and biomechanical driven process. Cardiovasc. Ther. 2021;2021:6642927. DOI: 10.1155/2021/6642927.

97. Avagimyan A., Fogacci F., Pogosova N., Kakturskiy L., Jndoyan Z., Faggiano A. et al. Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts. Curr. Probl. Cardiol. 2024;49(2):102230. DOI: 10.1016/j.cpcardiol.2023.102230.

98. Cuthbert G.A., Shaik F., Harrison M.A., Ponnambalam S., Homer-Vanniasinkam S. Scavenger receptors as biomarkers and therapeutic targets in cardiovascular disease. Cells. 2020;9(11):2453. DOI: 10.3390/cells9112453.

99. Kzhyshkowska J., Neyen C., Gordon S. Role of macrophage scavenger receptors in atherosclerosis. Immunobiology. 2012;217(5):492–502. DOI: 10.1016/j.imbio.2012.02.015.

100. Sun C.Q., Zhong C.Y., Sun W.W., Xiao H., Zhu P., Lin Y.Z. et al. Elevated type II secretory phospholipase A2 Increases the risk of early atherosclerosis in patients with newly diagnosed metabolic syndrome. Sci. Rep. 2016;6:34929. DOI: 10.1038/srep34929.

101. Kolodgie F.D., Gold H.K., Burke A.P., Fowler D.R., Kruth H.S., Weber D.K. et al. Intraplaque hemorrhage and progression of coronary atheroma. N. Engl. J. Med. 2003;349(24):2316–2325. DOI: 10.1056/NEJMoa035655.

102. Puylaert P., Zurek M., Rayner K.J., De Meyer G.R.Y., Martinet W. Regulated necrosis in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2022;42(11):1283–1306. DOI: 10.1161/ATVBAHA.122.318177.

103. Gillard B.K., Rosales C., Gotto A.M. Jr, Pownall H.J. The pathophysiology of excess plasma-free cholesterol. Curr. Opin. Lipidol. 2023;34(6):278–286. DOI: 10.1097/MOL.0000000000000899.