Clinical Physiology of Circulation

ISSN 1814-6910 (Print)
ISSN 2410-9134 (Online)

 

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Issue's catalogue ➤ КФК. 2025; 22 (3): 199-286 ➤ К проблеме неоваскуляризации каротидных атеросклеротических бляшек

On the problem of neovascularization of carotid atherosclerotic plaques

Authors: Shumilina M.V., Hayroyan A.G

Company:
Bakoulev National Medical Center for Cardiovascular Surgery, Moscow, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2025-22-3-236-248

UDC: 616.13-004.6-089

Link: Clinical Physiology of Blood Circulaiton. 2025; 22 (3): 236-248

Quote as: Shumilina M.V., Hayroyan A.G. On the problem of neovascularization of carotid atherosclerotic plaques. Clinical Physiology of Сirculation. 2025; 22 (3): 236–248 (in Russ.). DOI: 10.24022/1814-6910-2025-22-3-236-248

Keywords:  ultrasound contrast enhancement internal carotid arteries complicated plaque

Received / Accepted:  01.08.2025 / 15.08.2025

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Abstract

The article considers the relevance of studying the neovascularization of atherosclerotic plaques of the internal carotid arteries as a criterion of its complication. Pathomorphological features and possibilities of visualization of non-vessels are analyzed. The search was performed in PubMed, Сochranelibrary and Сyberleninka systems. Conclusions: All carotid plaques contain microvessels. With contrast enhancement of ultrasound examinations, neovascularization (CEUS) was detected in all plaques without significant differences between different types according to the classification of A. Gray-Weale. Hypoechoic plaques have higher degrees of neovascularization. The average diameter of the vessels that can be detected during CUSIS was 30 microns. The presence of “small” (< 20 microns) non-vessels indicates a high activity of the atherosclerotic (or even inflammatory) process; and the detection of “large” (> 40 microns) vessels indicates a high reparative potential and a sign of stabilization. The density of non-vessels is significantly higher in symptomatic than in asymptomatic plaques. Intra-plaque non-vessels in the middle region of carotid plaques are closely associated with symptomatic carotid stenosis, intra-plaque hemorrhage, and rupture of the fibrous cap. Symptomatic plaques significantly correlate with stronger contrast effects in luminal CUSIS than in adventitia (p = 0.0095). The registration of a high density of non-vessels in the plaque thickness is accompanied by an increased risk of developing end and intermediate points of patient observation; and the severity of calcification, connective tissue and lipid degeneration was not associated with a significant increase in the risk of cardiovascular complications. From the point of view of pathophysiology, it remains unclear whether vasa vasorum remodeling causes disease progression, controls it, or is a consequence of cardiovascular pathologies, as well as the issue of hemodynamics in non-vessels.

References

  1. Naylor R., Rantner B., Ancetti S., Borst G., Carlo M., Halliday A. et al. European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease. Eur. J. Vasc. Endovasc. Surg. 2023; 65 (1): 7–111. DOI: 10.1016/j.ejvs.2022.04.011
  2. Cao J., Zeng Y., Zhou Y., Yao Z., Tan Z., Huo G. et al. The value of contrast-enhanced ultrasound in assessing carotid plaque vulnerability and predicting stroke risk. Sci. Rep. 2025; 15 (1): 5850. DOI: 10.1038/s41598-025-90319-2
  3. Шейкина Н.А., Керен М.А., Сигаев И.Ю., Папиташвили В.Г., Чшиева И.В., Волковская И.В. и др. Отдаленные результаты коронарного шунтирования у больных с критическим каротидным стенозом в зависимости от выполнения этапной каротидной эндартерэктомии. Креативная кардиология. 2024; 18 (2): 225–238. DOI: 10.24022/1997-3187-2024-18-2-225-238
  4. Шумилина М.В., Спиридонов А.А., Бузиашвили Ю.И., Алекян Б.Г., Харпунов В.Ф. Приоритетность ультразвуковых методов диагностики в оценке состояния поверхности и размеров атеросклеротических бляшек внутренних сонных артерий. Грудная и сердечно-сосудистая хирургия. 1997; 4: 34–39.
  5. Бузиашвили Ю.И., Шумилина М.В., Арзуманян Р.С., Енокян Л.Г., Горбунова Е.В. О ключевых моментах ультразвуковой диагностики патологии брахиоцефальной системы. Сердечно-сосудистые заболевания. Бюллетень НЦССХ им. А.Н. Бакулева РАМН. 2009; 10 (1): 167–179.
  6. Шумилина М.В., Аракелян В.С., Дарвиш Н.А. Алгоритм ультразвукового обследования брахиоцефальных сосудов. Учебно- методическое пособие. М.: НМИЦ ССХ им. А.Н. Бакулева МЗ РФ; 2019.
  7. Шумилина М.В. Особенности ультразвуковой диагностики в ФГБУ «НМИЦ ССХ им. А.Н. Бакулева». Сердечно-сосудистые заболевания. Бюллетень НЦССХ им. А.Н. Бакулева РАМН. 2021; 22 (2): 184–195.
  8. Zamani M., Skagen K., Scott H., Lindberg B., Russell D., Skjelland M. Carotid plaque neovascularization detected with superb microvascular imaging ultrasound without using contrast media. Stroke. 2019; 50 (11): 3121–3127. DOI: 10.1161/STROKEAHA. 119.025496
  9. Щербак С.Г., Камилова Т.А., Лебедева С.В., Вологжанин Д.А., Голота А.С., Макаренко С.В., Апалько С.В. Биомаркеры каротидного стеноза. Физическая и реабилитационная медицина, медицинская реабилитация. 2021; 3 (1): 104–130. DOI: 10.36425/rehab64286
  10. Saba L., Cau R., Murgia A., Nicolaides A.N., Wintermark M., Castillo M. еt al. Carotid Plaque-RADS: a novel stroke risk classification system. JACC Cardiovasc. Imaging. 2024; 17 (1): 62–75. DOI: 10.1016/j.jcmg.2023.09.005
  11. Аракелян В.С., Щаницын И.Н., Андрейчук К.А., Балахонова Т.В., Балдин В.Л., Вачёв А.Н. и др. Окклюзия и стеноз сонной артерии (рекомендации российских экспертов). Ангиология и сосудистая хирургия. Журнал имени академика А.В. Покровского. 2025; 31 (2): 57–158. DOI: 10.33029/1027-6661-2025-31-2-57-158
  12. Kuzuya M. Effect of inflammatory cytokines and oxidized low density lipoprotein on vascular endothelial growth factor expression in macrophage. J. Japan. Geriatric. Society. 1998; 35 (4): 268–272. DOI: 10.3143/geriatrics.35.268
  13. Kwon H.M., Sangiorgi G., Ritman E.L., McKenna C., Holmes Jr., Schwartz R.S., Lerman A. Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. J. Clin. Invest. 1998; 101 (8): 1551–1556. DOI: 10.1172/JCI1568
  14. Moreno P.R., Purushothaman M., Purushothaman K.R. Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann. N. Y. Acad. Sci. 2012; 1254: 7–17. DOI: 10.1111/j.1749-6632.2012.06497.x
  15. Michel J.B., Martin-Ventura J.L., Nicoletti A., Ho-Tin-Noe B. Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages. Atherosclerosis. 2014; 234 (2): 311–319. DOI: 10.1016/j.atherosclerosis.2014.03.020
  16. Sluimer J.C., Kolodgie F., Bijnens A., Maxfield K., Pacheco E., Kutys B. et al. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J. Am. Coll. Cardiol. 2009; 53 (17): 1517–1527. DOI: 10.1016/j.jacc.2008.12.056
  17. Guo M., Cai Y., He C., Li Z. Coupled modeling of lipid deposition, inflammatory response and intraplaque angiogenesis in atherosclerotic plaque. Ann. Biomed. Eng. 2019; 47 (2): 439–452. DOI: 10.1007/s10439-018-02173-1
  18. Шумилина М.В., Заднепровская В.В., Ловрикова М.А. Неоваскуляризация при венозном тромбозе. Клиническая физиология кровообращения. 2023; 20 (2): 181–192. DOI: 10.24022/1814-6910-2023-20-2-181-192
  19. Liu Z., Zhang L., Sun B., Ding Y. Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque. Front. Neurol. 2024; 15: 1442656. DOI: 10.3389/fneur.2024. 1442656
  20. Пигаревский П.В., Ворожбит Р.А., Снегова В.А., Гусева В.А., Мальцева С.В., Давыдова Н.Г., Яковлева О.Г. Роль неоваскуляризации в формировании нестабильной атеросклеротической бляшки у человека. Архив патологии. 2021; 83 (3): 5–10. DOI: 10.17116/patol2021830315
  21. Zhai M., Sun X., Wang J., Xu J., Bian F., Wu M. et al. The Monocyte-to-Lymphocyte Ratio Was Associated With Intraplaque Neovascularization of the Carotid Artery on AngioPLUS. Brain Behav. 2024; 14 (10): e70058. DOI: 10.1002/brb3.70058
  22. Hellings W.E., Peeters W., Moll F.L., Piers S.R., Setten J., Spek P.J. et al. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation. 2010; 121 (17): 1941–1950. DOI: 10.1161/CIRCULATIONAHA.109.887497
  23. Liu Y., Fu X., Ai X., Li G., Wang C., Wu P. et al. Carotid Intraplaque neovascularization correlates with coronary atherosclerotic plaque, vulnerability detected by intracoronary optical coherence tomography. Int. J. Cardiol. 2025; 437: 133495. DOI: 10.1016/j.ijcard. 2025.133495
  24. Евдокименко А.Н., Чечеткин А.О., Друина Л.Д., Танашян М.М. Оценка неоваскуляризации атеросклеротической бляшки каротидного синуса с помощью контраст-усиленного УЗИ. Вестник РГМУ. 2019; 4: 25–33. DOI: 10.24075/vrgmu.2019.057
  25. Chen H., Peng C., Fang F., Li Y., Liu X., Hu Y. et al. Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis. Mechanobiol. Med. 2025; 3 (1): 100114. DOI: 10.1016/j.mbm.2025.100114
  26. Kumamoto M., Nakashima Y., Sueishi K. Intimal neovascularization in human coronary atherosclerosis: Its origin and pathophysiological significance. Human Pathology. 1995; 26 (4): 450–456. DOI: 10.1016/0046-8177(95)90148-5
  27. Phillippi J.A. On vasa vasorum: A history of advances in understanding the vessels of vessels. Sci. Adv. 2022; 8 (16): eabl6364. DOI: 10.1126/sciadv.abl6364
  28. Camaré C., Pucelle M., Nègre-Salvayre A., Salvayre R. Angiogenesis in the atherosclerotic plaque. Redox Biol. 2017; 12: 18–34. DOI: 10.1016/j.redox.2017.01.007
  29. Takeshita S., Inoue K., Ogata T., Ishii A., Uesugi N., Hamasaki M. et al. Impact of distribution of carotid intraplaque neovessels on plaque vulnerability. J. Stroke Cerebrovasc. Dis. 2024; 33 (10): 107859. DOI: 10.1016/j.jstrokecerebrovasdis.2024.107859
  30. Миронова О.Ю., Исайкина М.А., Исаев Г.О., Бердышева М.В., Фомин В.В. Ультразвуковые исследования с контрастированием: история, применение в практике и перспективы. Терапевтический архив. 2023; 95 (4): 354–358. DOI: 10.26442/00403660.2023. 04.202157
  31. https://www.vidal.ru/drugs/sonovue_40866
  32. Хамидова Л.Т., Рыбалко Н.В., Крылов В.В., Петриков С.С., Галанкина И.Е., Лукьянчиков В.А., Каниболоцкий А.А. Оценка нестабильности атеросклеротической бляшки в сонных артериях по результатам контрастно усиленного ультразвука и его корреляции с гистологическими исследованиями после каротидной эндартерэктомии. Журнал Диагностическая и интервенционная радиология. 2019; 13 (3): 26–35. DOI: 10.25512/DIR.2019.13.3.04
  33. Ермакова О.А., Умнов И.Н., Бобров А.Л., Китачев К.В., Чирский В.С., Пламинский Д.Ю. Оценка неоваскуляризации атеросклеротических бляшек каротидного синуса при помощи количественной перфузионной сонографии с контрастным усилением. Российский кардиологический журнал. 2020; 25 (5): 3825. DOI: 10.15829/1560-4071-2020-3825
  34. Zamani M., Skagen K., Lindberg B., Bjerkeli V., Auk-rust P., Halvorsen B., Skjelland M. Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: a pilot study. Front. Immunol. 2024; 15: 1385377. DOI: 10.3389/fimmu.2024.1385377
  35. Евдокименко А.Н., Куличенкова К.Н., Гулевская Т.С., Танашян М.М. Особенности регуляции ангиогенеза в атеросклеротических бляшках каротидного синуса на поздних стадиях развития атеросклероза. Российский физиологический журнал им. И.М. Сеченова. 2022; 108 (5): 649–666. DOI: 10.31857/S0869813922050041
  36. Uchihara Y., Saito K., Motoyama R., Ishibashi-Ueda H., Yamaguchi E., Hatakeyama K. et al. Neovascularization from the carotid artery lumen into the carotid plaque confirmed by contrast-enhanced ultrasound and histology. Ultrasound Med. Biol. 2023; 49 (8): 1798–1803. DOI: 10.1016/j.ultrasmedbio.2023.04.002
  37. Zhou S., Hui P. Predictive value of contrast-enhanced carotid ultrasound features for stroke risk: a systematic review and meta- analysis. Front. Neurol. 2025; 16: 1487850. DOI: 10.3389/fneur.2025.1487850
  38. Gimžauskaitė A., Trumpa E., Lukoševičius S., Plisienė J., Antuševas A., Velička L. et al. Assessment of atherosclerotic plaque morphology using contrast-enhanced ultrasound and its impact on primary cardiovascular events following simultaneous carotid endarterectomy and coronary artery bypass grafting. Vascular. 2025; 33 (1): 205–211. DOI: 10.1177/17085381241239499
  39. Lin C., Li X., Wu Y., Wang Y., Song W., Yan F., Sun L. Ultrasound molecular imaging of blood vessel walls and vulnerable plaques via CXCR4-targeted nanoscale GVs. Int. J. Nanomedicine. 2025; 20: 6205–6220. DOI: 10.2147/IJN.S504265
  40. Oliveira-Sousa J., Fragão-Marques M., Duarte-Gamas L., Ribeiro H., Rocha-Neves J. FGF-23 as a biomarker for carotid plaque vulnerability: a systematic review. Med. Sci. (Basel). 2025; 13 (1): 27. DOI: 10.3390/medsci13010027
  41. Školoudík D., Kešnerová P., Vomáčka J., Hrbáč T., Netuka D., Forostyak S. et al. ANTIQUE Trial Group. Shear-wave elastography enables identification of unstable carotid plaque. Ultrasound Med. Biol. 2021; 47 (7): 1704–1710. DOI: 10.1016/j.ultrasmedbio.2021. 03.026
  42. Chen Q., Wang W., Yuan C., Wang P. Research progress of matrix stiffness in regulating endothelial cell sprouting. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2023; 37 (2): 202–207 (in Chinese). DOI: 10.7507/1002-1892.202210019
  43. Van Hoof R.H., Heeneman S., Wildberger J.E., Kooi M.E. Dynamic contrast-enhanced MRI to study atherosclerotic plaque microvasculature. Curr. Atheroscler. Rep. 2016; 18 (6): 33. DOI: 10.1007/s11883-016-0583-4
  44. Tong W., Zhang Y., Hui H., Feng X., Ning B., Yu T. et al. Sensitive magnetic particle imaging of haemoglobin degradation for the detection and monitoring of intraplaque haemorrhage in atherosclerosis. EBioMedicine. 2023; 90: 104509. DOI: 10.1016/j.ebiom.2023.104509
  45. Chen W., Nadel J., Tumanov S., Stocker R. Near-Infrared Autofluorescence (NIRAF) in atherosclerotic plaque dissociates from intraplaque hemorrhage and bilirubin. Int. J. Mol. Sci. 2023; 24 (13): 10727. DOI: 10.3390/ijms241310727
  46. Hou C., Xuan J.Q., Zhao L., Li M.X., He W., Liu H. Comparison of the diagnostic performance of contrast-enhanced ultrasound and high-resolution magnetic resonance imaging in the evaluation of histologically defined vulnerable carotid plaque: a systematic review and meta-analysis. Quant Imaging Med. Surg. 2024; 14 (8): 5814–5830. DOI: 10.21037/qims-24-540
  47. Mézquita A.J.V., Biavati F., Falk V., Alkadhi H., Hajhosseiny R., Maurovich-Horvat P. et al. Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group. Nat. Rev. Cardiol. 2023; 20 (10): 696–714. DOI: 10.1038/s41569-023-00880-4
  48. Kuno T., Kiyohara Y., Maehara A., Ueyama H.A., Kampaktsis P.N., Takagi H. et al. Comparison of Intravascular Imaging, Functional, or Angiographically Guided Coronary Intervention. J. Am. Coll. Cardiol. 2023; 82 (23): 2167–2176. DOI: 10.1016/j.jacc.2023.09.823
  49. Мухамадияров Р.А., Клышников К.Ю., Кошелев В.А., Кутихин А.Г. Возможности электронно-микроскопической диагностики кальцификации, патологической неоваскуляризации и эластолиза в сочетании с фенотипированием клеточных популяций в крупных артериях. Российский кардиологический журнал. 2024; 29 (8): 5909. DOI: 10.15829/1560-4071-2024-5909
  50. Migdalski A., Jawien A. Neovascularization as a leading mechanism of intraplaque hemorrhage and carotid plaque destabilization: a narrative review. Curr. Vasc. Pharmacol. 2024; 22 (6): 377–385. DOI: 10.2174/0115701611304241240523045704
  51. Huang Y., Sun X., Ding X., Tan S., Yu Z., Shi X. et al. Pathological intraplaque hemorrhage as the gold standard to assess the efficacy of ultrasound in predicting vulnerable carotid plaque rupture. J. Ultrasound. Med. 2024; 43 (10): 1869–1881. DOI: 10.1002/jum.16518
  52. Zeng P., Zhang Q., Liang X., Zhang M., Luo D., Chen Z. Progress of ultrasound techniques in the evaluation of carotid vulnerable plaque neovascularization. Cerebrovasc. Dis. 2024; 53 (4): 479–487. DOI: 10.1159/000534372
****
  1. Naylor R., Rantner B., Ancetti S., Borst G., Carlo M., Halliday A. et al. European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease. Eur. J. Vasc. Endovasc. Surg. 2023; 65 (1): 7–111. DOI: 10.1016/j.ejvs.2022.04.011
  2. Cao J., Zeng Y., Zhou Y., Yao Z., Tan Z., Huo G. et al. The value of contrast-enhanced ultrasound in assessing carotid plaque vulnerability and predicting stroke risk. Sci. Rep. 2025; 15 (1): 5850. DOI: 10.1038/s41598-025-90319-2
  3. Sheikina N.A., Keren M.A., Sigaev I.Yu., Papitashvili V.G., Chshieva I.V., Volkovskaya I.V. et al. Long-term results of coronary bypass surgery in patients with critical carotid stenosis depending on the stage of carotid endarterectomy. Creative Cardiology. 2024; 18 (2): 225–238 (in Russ.). DOI: 10.24022/1997-3187-2024-18-2-225-238
  4. Shumilina M.V., Spiridonov A.A., Buziashvili Yu.I., Alekyan B.G., Kharpunov V.F. The priority of ultrasound diagnostic methods in assessing the condition of the surface and size of atherosclerotic plaques of the internal carotid arteries. Grudnaya i Serdechno- Sosudistaya Khirurgiya. 1997; 4: 34–39 (in Russ.).
  5. Buziashvili Yu.I., Shumilina M.V., Arzumanyan R.S., Enokyan L.G., Gorbunova E.V. On the key points of ultrasound diagnostics of pathology of the brachiocephalic system. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2009; 10 (1): 167–179 (in Russ.).
  6. Shumilina M.V., Arakelyan V.S., Darvish N.A. Algorithm of ultrasound examination of brachiocephalic vessels. Educational and methodical manual. Moscow; 2019 (in Russ.).
  7. Shumilina M.V. Features of ultrasound diagnostics at the Bakulev National Research Medical University. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2021; 22 (2): 184–195 (in Russ.).
  8. Zamani M., Skagen K., Scott H., Lindberg B., Russell D., Skjelland M. Carotid plaque neovascularization detected with superb microvascular imaging ultrasound without using contrast media. Stroke. 2019; 50 (11): 3121–3127. DOI: 10.1161/STROKEAHA. 119.025496
  9. Sсherbak S.G., Kamilova T.A., Lebedeva S.V., Vologzhanin D.A., Golota A.S., Makarenko S.V., Apalko S.V. Biomarkers of carotid stenosis. Physical and Rehabilitation Medicine, Medical Rehabilitation. 2021; 3 (1): 104–130 (in Russ.). DOI: 10.36425/rehab64286
  10. Saba L., Cau R., Murgia A., Nicolaides A.N., Wintermark M., Castillo M. еt al. Carotid Plaque-RADS: a novel stroke risk classification system. JACC Cardiovasc. Imaging. 2024; 17 (1): 62–75. DOI: 10.1016/j.jcmg.2023.09.005
  11. Arakelyan V.S., Shchanitsyn I.N., Andreychuk K.A., Balakhonova T.V., Baldin V.L., Vachev A.N. et al. Occlusion and stenosis of the carotid artery (recommendations of Russian experts). Angiology and Vascular Surgery. The journal named after Academician A.V. Pokrovsky. 2025; 31 (2): 57–158 (in Russ.). DOI: 10.33029/1027-6661-2025-31-2-57-158
  12. Kuzuya M. Effect of inflammatory cytokines and oxidized low density lipoprotein on vascular endothelial growth factor expression in macrophage. J. Japan. Geriatric. Society. 1998; 35 (4): 268–272. DOI: 10.3143/geriatrics.35.268
  13. Kwon H.M., Sangiorgi G., Ritman E.L., McKenna C., Holmes Jr., Schwartz R.S., Lerman A. Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. J. Clin. Invest. 1998; 101 (8): 1551–1556. DOI: 10.1172/JCI1568
  14. Moreno P.R., Purushothaman M., Purushothaman K.R. Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann. N. Y. Acad. Sci. 2012; 1254: 7–17. DOI: 10.1111/j.1749-6632.2012.06497.x
  15. Michel J.B., Martin-Ventura J.L., Nicoletti A., Ho-Tin-Noe B. Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages. Atherosclerosis. 2014; 234 (2): 311–319. DOI: 10.1016/j.atherosclerosis.2014.03.020
  16. Sluimer J.C., Kolodgie F., Bijnens A., Maxfield K., Pacheco E., Kutys B. et al. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J. Am. Coll. Cardiol. 2009; 53 (17): 1517–1527. DOI: 10.1016/j.jacc.2008.12.056
  17. Guo M., Cai Y., He C., Li Z. Coupled modeling of lipid deposition, inflammatory response and intraplaque angiogenesis in atherosclerotic plaque. Ann. Biomed. Eng. 2019; 47 (2): 439–452. DOI: 10.1007/s10439-018-02173-1
  18. Shumilina M.V., Zadneprovskaya V.V., Lovrikova M.A. Neovascularization in venous thrombosis. Clinical Physiology of Circulation. 2023; 20 (2): 181–192 (in Russ.). DOI: 10.24022/1814-6910-2023-20-2-181-192
  19. Liu Z., Zhang L., Sun B., Ding Y. Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque. Front. Neurol. 2024; 15: 1442656. DOI: 10.3389/fneur.2024. 1442656
  20. Pigarevsky P.V., Vorozhbit R.A., Snegova V.A., Guseva V.A., Maltseva S.V., Davydova N.G., Yakovleva O.G. The role of neovascularization in the formation of an unstable human atherosclerotic plaque. Russian Journal of Archive of Pathology. 2021; 83(3): 5–10 (in Russ.). DOI: 10.17116/patol2021830315
  21. Zhai M., Sun X., Wang J., Xu J., Bian F., Wu M. et al. The Monocyte-to-Lymphocyte Ratio Was Associated With Intraplaque Neovascularization of the Carotid Artery on AngioPLUS. Brain Behav. 2024; 14 (10): e70058. DOI: 10.1002/brb3.70058
  22. Hellings W.E., Peeters W., Moll F.L., Piers S.R., Setten J., Spek P.J. et al. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation. 2010; 121 (17): 1941–1950. DOI: 10.1161/CIRCULATIONAHA.109.887497
  23. Liu Y., Fu X., Ai X., Li G., Wang C., Wu P. et al. Carotid Intraplaque neovascularization correlates with coronary atherosclerotic plaque, vulnerability detected by intracoronary optical coherence tomography. Int. J. Cardiol. 2025; 437: 133495. DOI: 10.1016/j.ijcard. 2025.133495
  24. Evdokimenko A.N., Chechetkin A.O., Druina L.D., Tanashyan M.M. Assessment of neovascularization of atherosclerotic plaque of the carotid sinus using contrast enhanced ultrasound. Bulletin of the Russian State Medical University. 2019; 4: 25–33 (in Russ.). DOI: 10.24075/vrgmu.2019.057
  25. Chen H., Peng C., Fang F., Li Y., Liu X., Hu Y. et al. Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis. Mechanobiol. Med. 2025; 3 (1): 100114. DOI: 10.1016/j.mbm.2025.100114
  26. Kumamoto M., Nakashima Y., Sueishi K. Intimal neovascularization in human coronary atherosclerosis: Its origin and pathophysiological significance. Human Pathology. 1995; 26 (4): 450–456. DOI: 10.1016/0046-8177(95)90148-5
  27. Phillippi J.A. On vasa vasorum: A history of advances in understanding the vessels of vessels. Sci. Adv. 2022; 8 (16): eabl6364. DOI: 10.1126/sciadv.abl6364
  28. Camaré C., Pucelle M., Nègre-Salvayre A., Salvayre R. Angiogenesis in the atherosclerotic plaque. Redox Biol. 2017; 12: 18–34. DOI: 10.1016/j.redox.2017.01.007
  29. Takeshita S., Inoue K., Ogata T., Ishii A., Uesugi N., Hamasaki M. et al. Impact of distribution of carotid intraplaque neovessels on plaque vulnerability. J. Stroke Cerebrovasc. Dis. 2024; 33 (10): 107859. DOI: 10.1016/j.jstrokecerebrovasdis.2024.107859
  30. Mironova O.Yu., Isaikina M.A., Isaev G.O., Berdyshe-va M.V., Fomin V.V. Ultrasound examinations with contrast: history, practical application and prospects. Therapeutic Archive. 2023; 95 (4): 354–358 (in Russ.). DOI: 10.26442/00403660.2023.04.202157
  31. https://www.vidal.ru/drugs/sonovue_40866
  32. Khamidova L.T., Rybalko N.V., Krylov V.V., Petrikov S.S., Galankina I.E., Lukyanchikov V.A., Kanibolotsky A.A. Evaluation of atherosclerotic plaque instability in carotid arteries based on contrast-enhanced ultrasound and its correlation with histological studies after carotid endarterectomy. Journal Diagnostic and Interventional Radiology. 2019; 13 (3): 26–35. DOI: 10.25512/DIR.2019.13.3.04
  33. Ermakova O.A., Umnov I.N., Bobrov A.L., Kitachev K.V., Chirskiy V.S., Plaminsky D.Y. Assessment of neovascularization of atherosclerotic plaques of the carotid sinus using quantitative perfusion sonography with contrast enhancement. Russian Journal of Cardiology. 2020; 25 (5): 3825 (in Russ.). DOI: 10.15829/1560-4071-2020-3825
  34. Zamani M., Skagen K., Lindberg B., Bjerkeli V., Auk-rust P., Halvorsen B., Skjelland M. Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: a pilot study. Front. Immunol. 2024; 15: 1385377. DOI: 10.3389/fimmu.2024.1385377
  35. Evdokimenko A.N., Kulichenkova K.N., Gulevskaya T.S., Tanashyan M.M. Features of regulation of angiogenesis in atherosclerotic plaques of the carotid sinus in the late stages of atherosclerosis. I.M. Sechenov Russian Journal of Physiology. 2022; 108 (5): 649–666 (in Russ.). DOI: 10.31857/S0869813922050041
  36. Uchihara Y., Saito K., Motoyama R., Ishibashi-Ueda H., Yamaguchi E., Hatakeyama K. et al. Neovascularization from the carotid artery lumen into the carotid plaque confirmed by contrast-enhanced ultrasound and histology. Ultrasound Med. Biol. 2023; 49 (8): 1798–1803. DOI: 10.1016/j.ultrasmedbio.2023.04.002
  37. Zhou S., Hui P. Predictive value of contrast-enhanced carotid ultrasound features for stroke risk: a systematic review and meta- analysis. Front. Neurol. 2025; 16: 1487850. DOI: 10.3389/fneur.2025.1487850
  38. Gimžauskaitė A., Trumpa E., Lukoševičius S., Plisienė J., Antuševas A., Velička L. et al. Assessment of atherosclerotic plaque morphology using contrast-enhanced ultrasound and its impact on primary cardiovascular events following simultaneous carotid endarterectomy and coronary artery bypass grafting. Vascular. 2025; 33 (1): 205–211. DOI: 10.1177/17085381241239499
  39. Lin C., Li X., Wu Y., Wang Y., Song W., Yan F., Sun L. Ultrasound molecular imaging of blood vessel walls and vulnerable plaques via CXCR4-targeted nanoscale GVs. Int. J. Nanomedicine. 2025; 20: 6205–6220. DOI: 10.2147/IJN.S504265
  40. Oliveira-Sousa J., F ragão-Marques M., Duarte-Gamas L., Ribeiro H., Rocha-Neves J. FGF-23 as a biomarker for carotid plaque vulnerability: a systematic review. Med. Sci. (Basel). 2025; 13 (1): 27. DOI: 10.3390/medsci13010027
  41. Školoudík D., Kešnerová P., Vomáčka J., Hrbáč T., Netuka D., Forostyak S. et al. ANTIQUE Trial Group. Shear-wave elastography enables identification of unstable carotid plaque. Ultrasound Med. Biol. 2021; 47 (7): 1704–1710. DOI: 10.1016/j.ultrasmedbio.2021. 03.026
  42. Chen Q., Wang W., Yuan C., Wang P. Research progress of matrix stiffness in regulating endothelial cell sprouting. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2023; 37 (2): 202–207 (in Chinese). DOI: 10.7507/1002-1892.202210019
  43. Van Hoof R.H., Heeneman S., Wildberger J.E., Kooi M.E. Dynamic contrast-enhanced MRI to study atherosclerotic plaque microvasculature. Curr. Atheroscler. Rep. 2016; 18 (6): 33. DOI: 10.1007/s11883-016-0583-4
  44. Tong W., Zhang Y., Hui H., Feng X., Ning B., Yu T. et al. Sensitive magnetic particle imaging of haemoglobin degradation for the detection and monitoring of intraplaque haemorrhage in atherosclerosis. EBioMedicine. 2023; 90: 104509. DOI: 10.1016/j.ebiom.2023.104509
  45. Chen W., Nadel J., Tumanov S., Stocker R. Near-Infrared Autofluorescence (NIRAF) in atherosclerotic plaque dissociates from intraplaque hemorrhage and bilirubin. Int. J. Mol. Sci. 2023; 24 (13): 10727. DOI: 10.3390/ijms241310727
  46. Hou C., Xuan J.Q., Zhao L., Li M.X., He W., Liu H. Comparison of the diagnostic performance of contrast-enhanced ultrasound and high-resolution magnetic resonance imaging in the evaluation of histologically defined vulnerable carotid plaque: a systematic review and meta-analysis. Quant Imaging Med. Surg. 2024; 14 (8): 5814–5830. DOI: 10.21037/qims-24-540
  47. Mézquita A.J.V., Biavati F., Falk V., Alkadhi H., Hajhosseiny R., Maurovich-Horvat P. et al. Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group. Nat. Rev. Cardiol. 2023; 20 (10): 696–714. DOI: 10.1038/s41569-023-00880-4
  48. Kuno T., Kiyohara Y., Maehara A., Ueyama H.A., Kampaktsis P.N., Takagi H. et al. Comparison of Intravascular Imaging, Functional, or Angiographically Guided Coronary Intervention. J. Am. Coll. Cardiol. 2023; 82 (23): 2167–2176. DOI: 10.1016/j.jacc.2023.09.823
  49. Mukhamadiyarov R.A., Klyshnikov K.Yu., Koshelev V.A., Kutikhin A.G. Possibilities of electron microscopic diagnostics of calcification, pathological neovascularization and elastolysis in combination with phenotyping of cell populations in large arteries. Russian Journal of Cardiology. 2024; 29 (8): 5909(in Russ.). DOI: 10.15829/1560-4071-2024-5909
  50. Migdalski A., Jawien A. Neovascularization as a leading mechanism of intraplaque hemorrhage and carotid plaque destabilization: a narrative review. Curr. Vasc. Pharmacol. 2024; 22 (6): 377–385. DOI: 10.2174/0115701611304241240523045704
  51. Huang Y., Sun X., Ding X., Tan S., Yu Z., Shi X. et al. Pathological intraplaque hemorrhage as the gold standard to assess the efficacy of ultrasound in predicting vulnerable carotid plaque rupture. J. Ultrasound. Med. 2024; 43 (10): 1869–1881. DOI: 10.1002/jum.16518
  52. Zeng P., Zhang Q., Liang X., Zhang M., Luo D., Chen Z. Progress of ultrasound techniques in the evaluation of carotid vulnerable plaque neovascularization. Cerebrovasc. Dis. 2024; 53 (4): 479–487. DOI: 10.1159/000534372

About Authors

  • Margarita V. Shumilina, Dr. Med. Sci., Head of the Ultrasound Diagnostics Department, Ultrasonic Diagnostician, Professor of the Department of Cardiology, Ultrasound and Functional Diagnostics with a course in Pediatric Cardiology; ORCID
  • Astine G. Hayroyan, Ultrasonic Diagnostician; ORCID

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