nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2025-12-1-55-61nodgo-1131Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSЭндотелиальная дисфункция как фактор риска тромботических осложнений у детей с послеоперационным тромбоцитозом (обзор литературы)Endothelial dysfunction as a risk factor for thrombotic complications in children with postoperative thrombocytosis (literature review)БровкинаЕ. А.BrovkinaE. A.

Евгения Аркадьевна Бровкина - врач-гематолог консультативного отделения 

117997, Москва, ул. Саморы Машела, 1

Hematologist of the Consultative Department

1 Samory Mashela St., Moscow, 117997

evgenia.brovkina@dgoi.ruФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава РоссииРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian Federation2025230420251215561Copyright © Бровкина Е.А., 20252025Бровкина Е.А.Brovkina E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/1131

Эндотелиальная дисфункция (ЭД) – ключевое звено в развитии тромботических осложнений и сердечно-сосудистых заболеваний. В статье рассмотрены биохимические и молекулярные механизмы ЭД. Особое внимание уделено роли ЭД в развитии тромбозов у пациентов после спленэктомии. У детей ЭД может быть вызвана врожденными патологиями, хроническими заболеваниями или хирургическими вмешательствами, что делает проблему особенно актуальной в педиатрии. Описаны современные методы диагностики, а также их ограничения в педиатрической практике. Рассмотрены потенциальные терапевтические подходы, однако единые стандарты лечения отсутствуют. Статья акцентирует внимание на важности изучения ЭД как значимого фактора риска, требующего новых подходов в педиатрии и детской гематологии.

Endothelial dysfunction (ED) is a key factor in the development of thrombotic complications and cardiovascular diseases. The article examines the biochemical and molecular mechanisms of ED. Special attention is given to the role of ED in the development of thrombosis in patients after splenectomy. In children, ED can be caused by congenital pathologies, chronic diseases, or surgical interventions, making this issue particularly relevant in pediatrics. Modern diagnostic methods are described, along with their limitations in pediatric practice. Potential therapeutic approaches are discussed, although standardized treatment protocols are lacking. The article emphasizes the importance of studying ED as a significant risk factor that requires new approaches in pediatrics and pediatric hematology.

эндотелиальная дисфункциятромботические осложненияспленэктомияоксид азотаоксидативный стресссистемное воспалениедиагностикатромбоцитоздетская гематологияendothelial dysfunctionthrombotic complicationssplenectomynitric oxideoxidative stresssystemic inflammationdiagnosisthrombocytosispediatric hematologyReferencesШилов А.В., Мнихович М.В., Калинин Р.Е., Сучков И.А., Кактурский Л.В., Рудницкий С.В., Нечаев Л.В. Морфологические изменения стенки сосудов при эндотелиальной дисфункции. Журнал анатомии и гистопатологии. 2017;6(2):115–21. doi: 10.18499/22257357-2017-6-2-115-121.Shilov A.V., Mnikhovich M.V., Kalinin R.E., Suchkov I.A., Kakturskiy L.V., Rudnitskiy S.V., Nechaev L.V. Morphological changes in the wall of vessels in endothelial dysfunction. Zhurnal anatomii i gistopatologii = Journal of Anatomy and Histopathology. 2017;6(2):115–21. (In Russ.)].Раваева М.Ю., Чуян Е.Н., Древетняк Н.А. Роль оксида азота в развитии эндотелиальной дисфункции. Ученые записки Крымского федерального университета им. В.И. Вернадского. Биология. Химия. 2013;26(4(65)):147–57.Ravaeva M.Yu., Chuyan E.N., Drevetnyak N.A. The role of nitric oxide in the development of endothelial dysfunction. Uchenyye zapiski Krymskogo federalʼnogo universiteta imeni V.I. Vernadskogo. Biologiya. Khimiya = Scientifi c Notes of V.I. Vernadsky Crimean Federal University. Biology. Chemistry. 2013;26(4(65)):147–57. (In Russ.)].Радайкина О.Г., Власов А.П., Мышкина Н.А. Роль эндотелиальной дисфункции в патологии сердечно-сосудистой системы. Ульяновский медико-биологический журнал. 2018;(4):8–17.Radaykina O.G., Vlasov A.P., Myshkina N.A. Role of endothelial dysfunction in cardiovascular system pathology. Ulʼyanovskiy mediko-biologicheskiy zhurnal = Ulyanovsk Medico-biological Journal. 2018;(4):8–17. (In Russ.)].Theofi lis P., Sagris M., Oikonomou E., Antonopoulos A.S., Siasos G., Tsioufi s C., Tousoulis D. Infl ammatory Mechanisms Contributing to Endothelial Dysfunction. Biomedicines. 2021;9(7):781. doi: 10.3390/biomedicines9070781.Theofi lis P., Sagris M., Oikonomou E., Antonopoulos A.S., Siasos G., Tsioufi s C., Tousoulis D. Infl ammatory Mechanisms Contributing to Endothelial Dysfunction. Biomedicines. 2021;9(7):781. doi: 10.3390/biomedicines9070781.Wybranska I. Genetic Markers of Endothelial Dysfunction. Endothelial Dysfunction – A Novel Paradigm. Published online. doi: 10.5772/intechopen.109272. [Electronic resource]: https://www.intechopen.com/chapters/85824.Wybranska I. Genetic Markers of Endothelial Dysfunction. Endothelial Dysfunction – A Novel Paradigm. Published online. doi: 10.5772/intechopen.109272. [Electronic resource]: https://www.intechopen.com/chapters/85824.Çiftel M., Ataş N., Yılmaz O. Investigation of endothelial dysfunction and arterial stiff ness in multisystem infl ammatory syndrome in children. Eur J Pediatr. 2022;181(1):91–7. doi: 10.1007/s00431-021-04136-6.Çiftel M., Ataş N., Yılmaz O. Investigation of endothelial dysfunction and arterial stiff ness in multisystem infl ammatory syndrome in children. Eur J Pediatr. 2022;181(1):91–7. doi: 10.1007/s00431-021-04136-6.Lee W.F., Wu C.Y., Yang H.Y., Lee W.I., Chen L.C., Ou L.S., Huang J.L. Biomarkers associating endothelial dysregulation in pediatric-onset systemic lupus erythematous. Pediatr Rheumatol Online J. 2019;17(1):69. doi: 10.1186/s12969-019-0369-7.Lee W.F., Wu C.Y., Yang H.Y., Lee W.I., Chen L.C., Ou L.S., Huang J.L. Biomarkers associating endothelial dysregulation in pediatric-onset systemic lupus erythematous. Pediatr Rheumatol Online J. 2019;17(1):69. doi: 10.1186/s12969-019-0369-7.Chia Y.C., Siti Asmaa M.J., Ramli M., Woon P.Y., Johan M.F., Hassan R., Islam M.A. Molecular Genetics of Thrombotic Myeloproliferative Neoplasms: Implications in Precision Oncology. Diagnostics (Basel). 2023;13(1):163. doi: 10.3390/diagnostics13010163.Chia Y.C., Siti Asmaa M.J., Ramli M., Woon P.Y., Johan M.F., Hassan R., Islam M.A. Molecular Genetics of Thrombotic Myeloproliferative Neoplasms: Implications in Precision Oncology. Diagnostics (Basel). 2023;13(1):163. doi: 10.3390/diagnostics13010163.Genovesi S., Giussani M., Orlando A., Lieti G., Viazzi F., Parati G. Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents. Pediatr Nephrol. 2022;37(3):537–45. doi: 10.1007/s00467-021-05144-2.Genovesi S., Giussani M., Orlando A., Lieti G., Viazzi F., Parati G. Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents. Pediatr Nephrol. 2022;37(3):537–45. doi: 10.1007/s00467-021-05144-2.Степанова Т.В., Иванов А.Н., Терешкина Н.Е., Попыхова Э.Б., Лагутина Д.Д. Маркеры эндотелиальной дисфункции: патогенетическая роль и диагностическое значение (обзор литературы). Клиническая лабораторная диагностика. 2019;64(1):34–41. doi: 10.18821/0869-2084-2019-64-34-41.Stepanova T.V., Ivanov A.N., Tereshkina N.E., Popiekhova E.B., Lagutina D.D. Markers of endothelial dysfunction: pathogenetic role and diagnostic signifi cance. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics. 2019;64(1):34–41. (In Russ.)].Cersosimo E., DeFronzo R.A. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev. 2006;22(6):423–36. doi: 10.1002/dmrr.634. PMID: 16506274.Cersosimo E., DeFronzo R.A. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev. 2006;22(6):423–36. doi: 10.1002/dmrr.634. PMID: 16506274.Krenning G., Barauna V.G., Krieger J.E., Harmsen M.C., Moonen J.R. Endothelial Plasticity: Shifting Phenotypes through Force Feedback. Stem Cells Int. 2016;2016:9762959. doi: 10.1155/2016/9762959.Krenning G., Barauna V.G., Krieger J.E., Harmsen M.C., Moonen J.R. Endothelial Plasticity: Shifting Phenotypes through Force Feedback. Stem Cells Int. 2016;2016:9762959. doi: 10.1155/2016/9762959.Csiszar A., Tarantini S., Yabluchanskiy A., Balasubramanian P., Kiss T., Farkas E., Baur J.A., Ungvari Z. Role of endothelial NAD+ defi ciency in age-related vascular dysfunction. Am J Physiol Heart Circ Physiol. 2019;316(6):H1253–66. doi: 10.1152/ajpheart.00039.2019.Csiszar A., Tarantini S., Yabluchanskiy A., Balasubramanian P., Kiss T., Farkas E., Baur J.A., Ungvari Z. Role of endothelial NAD+ defi ciency in age-related vascular dysfunction. Am J Physiol Heart Circ Physiol. 2019;316(6):H1253–66. doi: 10.1152/ajpheart.00039.2019.Inostroza-Nieves Y., Rivera A., Romero J.R. Blockade of endothelin-1 receptor B regulates molecules of the major histocompatibility complex in sickle cell disease. Front Immunol. 2023;14:1124269. doi: 10.3389/fimmu.2023.1124269.Inostroza-Nieves Y., Rivera A., Romero J.R. Blockade of endothelin-1 receptor B regulates molecules of the major histocompatibility complex in sickle cell disease. Front Immunol. 2023;14:1124269. doi: 10.3389/fimmu.2023.1124269.Victor V.M., Rocha M., Solá E., Bañuls C., Garcia-Malpartida K., Hernández-Mijares A. Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des. 2009;15(26):2988–3002. doi: 10.2174/138161209789058093.Victor V.M., Rocha M., Solá E., Bañuls C., Garcia-Malpartida K., Hernández-Mijares A. Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des. 2009;15(26):2988–3002. doi: 10.2174/138161209789058093.Zhang G., Yu H., Su J., Chi C., Su L., Wang F., Zheng Y., Xie B., Kang K. Identifi cation of Key Genes Associated with Endothelial Cell Dysfunction in Atherosclerosis Using Multiple Bioinformatics Tools. Biomed Res Int. 2022;2022:5544276. doi: 10.1155/2022/5544276.Zhang G., Yu H., Su J., Chi C., Su L., Wang F., Zheng Y., Xie B., Kang K. Identifi cation of Key Genes Associated with Endothelial Cell Dysfunction in Atherosclerosis Using Multiple Bioinformatics Tools. Biomed Res Int. 2022;2022:5544276. doi: 10.1155/2022/5544276.Aoyama R., Kubota Y., Tara S., Wakita S., Yamaguchi H., Shimizu W., Takano H. Vascular Endothelial Dysfunction in Myeloproliferative Neoplasms and Gene Mutations. Int Heart J. 2022;63(4):661–8. doi: 10.1536/ihj.22-003.Aoyama R., Kubota Y., Tara S., Wakita S., Yamaguchi H., Shimizu W., Takano H. Vascular Endothelial Dysfunction in Myeloproliferative Neoplasms and Gene Mutations. Int Heart J. 2022;63(4):661–8. doi: 10.1536/ihj.22-003.Zhang G., Yu H., Su J., Chi C., Su L., Wang F., Zheng Y., Xie B., Kang K. Identifi cation of Key Genes Associated with Endothelial Cell Dysfunction in Atherosclerosis Using Multiple Bioinformatics Tools. Biomed Res Int. 2022;2022:5544276. doi: 10.1155/2022/5544276.Zhang G., Yu H., Su J., Chi C., Su L., Wang F., Zheng Y., Xie B., Kang K. Identifi cation of Key Genes Associated with Endothelial Cell Dysfunction in Atherosclerosis Using Multiple Bioinformatics Tools. Biomed Res Int. 2022;2022:5544276. doi: 10.1155/2022/5544276.Chirkov Y.Y., Nguyen T.H., Horowitz J.D. Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease. Int J Mol Sci. 2022;23(3):1042. doi: 10.3390/ijms23031042.Chirkov Y.Y., Nguyen T.H., Horowitz J.D. Impairment of AntiAggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease. Int J Mol Sci. 2022;23(3):1042. doi: 10.3390/ijms23031042.Kohli S., Shahzad K., Jouppila A., Holthöfer H., Isermann B., Lassila R. Thrombosis and Infl ammation-A Dynamic Interplay and the Role of Glycosaminoglycans and Activated Protein C. Front Cardiovasc Med. 2022;9:866751. doi: 10.3389/fcvm.2022.866751.Kohli S., Shahzad K., Jouppila A., Holthöfer H., Isermann B., Lassila R. Thrombosis and Infl ammation-A Dynamic Interplay and the Role of Glycosaminoglycans and Activated Protein C. Front Cardiovasc Med. 2022;9:866751. doi: 10.3389/fcvm.2022.866751.Castiglione M., Jiang Y.-P., Mazzeo C., Lee S., Chen J.-S., Kaushansky K., Yin W., Lin R.Z., Zheng H., Zhan H. Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm. J Thromb Haemost. 2020;18(12):3359–70. doi: 10.1111/jth.15095.Castiglione M., Jiang Y.-P., Mazzeo C., Lee S., Chen J.-S., Kaushansky K., Yin W., Lin R.Z., Zheng H., Zhan H. Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm. J Thromb Haemost. 2020;18(12):3359–70. doi: 10.1111/jth.15095.Mahmood I., Hamdan F., Al-Tameemi W. Role of endothelial dysfunction in relation to prothrombogenesis in polycythemia vera. Iraqi J Hematol. 2018;7:8. doi:10.4103/IJH.IJH_32_17.Mahmood I., Hamdan F., Al-Tameemi W. Role of endothelial dysfunction in relation to prothrombogenesis in polycythemia vera. Iraqi J Hematol. 2018;7:8. doi:10.4103/IJH.IJH_32_17.Baldauf C.K., Charakopoulos E., Böttcher M., Zeremski V., Mougiakakos D., Schraven B., Fischer T. JAK2-V617F Promotes up-Regulation of Pro-Infl ammatory Cytokines Including IL-1 upon Adhesion-Induced Activation of β1/β2 Integrins. Blood 2023;142(Suppl 1):2749. doi: 10.1182/blood-2023-174058.Baldauf C.K., Charakopoulos E., Böttcher M., Zeremski V., Mougiakakos D., Schraven B., Fischer T. JAK2-V617F Promotes up-Regulation of Pro-Infl ammatory Cytokines Including IL-1 upon Adhesion-Induced Activation of β1/β2 Integrins. Blood 2023;142(Suppl 1):2749. doi: 10.1182/blood-2023-174058.Rajendran P., Rengarajan T., Thangavel J. The Vascular Endothelium and Human Diseases. Int J Biol Sci. 2013;9:1057. doi: 10.7150/IJBS.7502.Rajendran P., Rengarajan T., Thangavel J. The Vascular Endothelium and Human Diseases. Int J Biol Sci. 2013;9:1057. doi: 10.7150/IJBS.7502.Saghazadeh A., Rezaei N. Infl ammation as a cause of venous thromboembolism. Crit Rev Oncol Hematol. 2016;99:272–85. doi: 10.1016/J.CRITREVONC.2016.01.007.Saghazadeh A., Rezaei N. Infl ammation as a cause of venous thromboembolism. Crit Rev Oncol Hematol. 2016;99:272–85. doi: 10.1016/J.CRITREVONC.2016.01.007.Ejikeme C., Elkattawy S., Kayode-Ajala F. Reactive thrombocytosis after splenectomy in hereditary spherocytosis: Case report and literature review. Eur J Case Rep Intern Med. 2021;8. doi: 10.12890/2021_002673.Ejikeme C., Elkattawy S., Kayode-Ajala F. Reactive thrombocytosis after splenectomy in hereditary spherocytosis: Case report and literature review. Eur J Case Rep Intern Med. 2021;8. doi: 10.12890/2021_002673.Stringer M.D., Lucas N. Thrombocytosis and portal vein thrombosis after splenectomy for paediatric haemolytic disorders: How should they be managed? J Paediatr Child Health. 2018;54:1184–8. doi: 10.1111/jpc.14227.Stringer M.D., Lucas N. Thrombocytosis and portal vein thrombosis after splenectomy for paediatric haemolytic disorders: How should they be managed? J Paediatr Child Health. 2018;54:1184–8. doi: 10.1111/jpc.14227.Zulkafl i Z., Janaveloo T., Rahman W.S.W.A. Extreme thrombocytosis in a child: Laboratory approaches and diagnostic challenges. Oman Med J. 2019;34:336–40. doi: 10.5001/omj.2019.65.Zulkafl i Z., Janaveloo T., Rahman W.S.W.A. Extreme thrombocytosis in a child: Laboratory approaches and diagnostic challenges. Oman Med J. 2019;34:336–40. doi: 10.5001/omj.2019.65.Rodeghiero F., Ruggeri M. Short- and long-term risks of splenectomy for benign haematological disorders: should we revisit the indications? Br J Haematol. 2012;158(1):16–29. doi: 10.1111/J.1365-2141.2012.09146.X.Rodeghiero F., Ruggeri M. Short- and long-term risks of splenectomy for benign haematological disorders: should we revisit the indications? Br J Haematol. 2012;158(1):16–29. doi: 10.1111/J.1365-2141.2012.09146.X.Ferrara M., Bertocco F., Ferrara D., Capozzi L. Postsplenectomy Thromboembolic Risk in Children with Hematologic Disorders: Case Report. J Blood Disord Transfus. 2014;5(8). doi: 10.4172/2155-9864.1000225.Ferrara M., Bertocco F., Ferrara D., Capozzi L. Postsplenectomy Thromboembolic Risk in Children with Hematologic Disorders: Case Report. J Blood Disord Transfus. 2014;5(8). doi: 10.4172/2155-9864.1000225.Troendle S.B., Adix L., Crary S.E., Buchanan G.R. Laboratory markers of thrombosis risk in children with hereditary spherocytosis. Pediatr Blood Cancer. 2007;49(6):781–5. doi: 10.1002/pbc.21319.Troendle S.B., Adix L., Crary S.E., Buchanan G.R. Laboratory markers of thrombosis risk in children with hereditary spherocytosis. Pediatr Blood Cancer. 2007;49(6):781–5. doi: 10.1002/pbc.21319.Autoimmune Thrombocytopenia. Y. Ishida, Y. Tomiyama (eds.) Springer Nature Singapore Pte Ltd., 2017. Pp. 159–64. doi: 10.1007/978-981-10-4142-6_15.Autoimmune Thrombocytopenia. Y. Ishida, Y. Tomiyama (eds.) Springer Nature Singapore Pte Ltd., 2017. Pp. 159–64. doi: 10.1007/978-981-10-4142-6_15.Guo B., Pan J., Shen Y., Zhang Q., Wang Z., Huang L., Yu Q. Plateletʼs Rule of Change and Clinical Signifi cance before and after Splenectomy. Am J Surg. 2019;1;85(11):1288–93. PMID: 31775973.Guo B., Pan J., Shen Y., Zhang Q., Wang Z., Huang L., Yu Q. Plateletʼs Rule of Change and Clinical Signifi cance before and after Splenectomy. Am J Surg. 2019;1;85(11):1288–93. PMID: 31775973.Zvizdic Z., Kovacevic A., Milisic E., Jonuzi A., Vranic S. Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country. PLoS One. 2020;15(8):e0237016. doi: 10.1371/journal.pone.0237016.Zvizdic Z., Kovacevic A., Milisic E., Jonuzi A., Vranic S. Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country. PLoS One. 2020;15(8):e0237016. doi: 10.1371/journal.pone.0237016.Gelas T., Scalabre A., Hameury F., Dubois R., Grosos C., Mouriquand P.D., Mure P.-Y. Portal vein thrombosis after laparoscopic splenectomy during childhood. J Thromb Thrombolysis. 2014;38:218–22. doi: 10.1007/s11239-013-1037-2.Gelas T., Scalabre A., Hameury F., Dubois R., Grosos C., Mouriquand P.D., Mure P.-Y. Portal vein thrombosis after laparoscopic splenectomy during childhood. J Thromb Thrombolysis. 2014;38:218–22. doi: 10.1007/s11239-013-1037-2.Krauth M., Lechner K., Neugebauer E.A.M., Pabinger I. The postoperative splenic/portal vein thrombosis after splenectomy and its prevention – an unresolved issue. Haematologica. 2008;93(8):1227–32. doi: 10.3324/haematol.12682.Krauth M., Lechner K., Neugebauer E.A.M., Pabinger I. The postoperative splenic/portal vein thrombosis after splenectomy and its prevention – an unresolved issue. Haematologica. 2008;93(8):1227–32. doi: 10.3324/haematol.12682.Leite A.R., Borges-Canha M., Cardoso R., Neves J.S., Castro-Ferreira R., Leite-Moreira A. Novel Biomarkers for Evaluation of Endothelial Dysfunction. Angiology. 2020;71(5):397–410. doi: 10.3324/haematol.12682.Leite A.R., Borges-Canha M., Cardoso R., Neves J.S., Castro-Ferreira R., Leite-Moreira A. Novel Biomarkers for Evaluation of Endothelial Dysfunction. Angiology. 2020;71(5):397–410. doi: 10.3324/haematol.12682.Gragnano F., Sperlongano S., Golia E., Natale F., Bianchi R., Crisci M., Fimiani F., Pariggiano I., Diana V., Carbone A., Cesaro A., Concilio C., Limongelli G., Russo M., Calabrò P. The Role of von Willebrand Factor in Vascular Infl ammation: From Pathogenesis to Targeted Therapy. Mediators Infl amm. 2017;2017:5620314. doi: 10.1155/2017/5620314.Gragnano F., Sperlongano S., Golia E., Natale F., Bianchi R., Crisci M., Fimiani F., Pariggiano I., Diana V., Carbone A., Cesaro A., Concilio C., Limongelli G., Russo M., Calabrò P. The Role of von Willebrand Factor in Vascular Infl ammation: From Pathogenesis to Targeted Therapy. Mediators Infl amm. 2017;2017:5620314. doi: 10.1155/2017/5620314.Rodriguez-Miguelez P., Seigler N., Harris R.A. Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test. J Vis Exp. 2016;(110):54011. doi: 10.3791/54011.Rodriguez-Miguelez P., Seigler N., Harris R.A. Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test. J Vis Exp. 2016;(110):54011. doi: 10.3791/54011.Hopkins N.D., Dengel D.R., Stratton G., Kelly A.S., Steinberger J., Zavala H., Marlatt K., Perry D., Naylor L.H., Green D.J. Age and sex relationship with fl ow-mediated dilation in healthy children and adolescents. J Appl Physiol. 2015;119(8):926–33. doi: 10.1152/japplphysiol.01113.2014.Hopkins N.D., Dengel D.R., Stratton G., Kelly A.S., Steinberger J., Zavala H., Marlatt K., Perry D., Naylor L.H., Green D.J. Age and sex relationship with fl ow-mediated dilation in healthy children and adolescents. J Appl Physiol. 2015;119(8):926–33. doi: 10.1152/japplphysiol.01113.2014.Evanoff N.G., Kelly A.S., Steinberger J., Dengel D.R. Peak Shear and Peak Flow Mediated Dilation: A Time Course Relationship. J Clin Ultrasound. 2016;44(3):182. doi: 10.1002/JCU.22324.Evanoff N.G., Kelly A.S., Steinberger J., Dengel D.R. Peak Shear and Peak Flow Mediated Dilation: A Time Course Relationship. J Clin Ultrasound. 2016;44(3):182. doi: 10.1002/JCU.22324.Jakubowski M., Turek-Jakubowska A., Szahidewicz-Krupska E., Gawrys K., Gawrys J., Doroszko A. Profi ling the endothelial function using both peripheral artery tonometry (EndoPAT) and Laser Doppler Flowmetry (LD) – Complementary studies or waste of time? Microvasc Res. 2020;130:104008. doi: 10.1016/J.MVR.2020.104008.Jakubowski M., Turek-Jakubowska A., Szahidewicz-Krupska E., Gawrys K., Gawrys J., Doroszko A. Profi ling the endothelial function using both peripheral artery tonometry (EndoPAT) and Laser Doppler Flowmetry (LD) – Complementary studies or waste of time? Microvasc Res. 2020;130:104008. doi: 10.1016/J.MVR.2020.104008.Dri E., Lampas E., Lazaros G., Lazarou E., Theofi lis P., Tsioufi s C., Tousoulis D. Infl ammatory Mediators of Endothelial Dysfunction. Life. 2023;13(6):1420. doi: 10.3390/life13061420.Dri E., Lampas E., Lazaros G., Lazarou E., Theofi lis P., Tsioufi s C., Tousoulis D. Infl ammatory Mediators of Endothelial Dysfunction. Life. 2023;13(6):1420. doi: 10.3390/life13061420.Kutikhin A., Shishkova D., Velikanova E., Sinitsky M.Yu., Sinitskaya A.V., Markova V.E. Endothelial Dysfunction in the Context of Blood–Brain Barrier Modeling. J Evol Biochem Phys. 2022;58:781–806. doi: 10.1134/S0022093022030139.Kutikhin A., Shishkova D., Velikanova E., Sinitsky M.Yu., Sinitskaya A.V., Markova V.E. Endothelial Dysfunction in the Context of Blood–Brain Barrier Modeling. J Evol Biochem Phys. 2022;58:781–806. doi: 10.1134/S0022093022030139.Hafsari A., Ridha N.R. Reactive trhombocytosis in children. Int J Health Sci Med Res. 2022;1(2):111–32. doi: 10.37905/ijhsmr.v1i2.14134.Hafsari A., Ridha N.R. Reactive trhombocytosis in children. Int J Health Sci Med Res. 2022;1(2):111–32. doi: 10.37905/ijhsmr.v1i2.14134.Deshpande D., Janero D., Amiji M. Therapeutic strategies for endothelial dysfunction. Expert Opin Biol Ther. 2011;11(12):1637–54. doi: 10.1517/14712598.2011.625007.Deshpande D., Janero D., Amiji M. Therapeutic strategies for endothelial dysfunction. Expert Opin Biol Ther. 2011;11(12):1637–54. doi: 10.1517/14712598.2011.625007.De Jongh S., Lilien M.R., Op’T Roodt J., Stroes E.S.G., Bakker H.D., Kastelein J.J.P. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol. 2002;40(12):2117–21. doi: 10.1016/S0735-1097(02)02593-7.De Jongh S., Lilien M.R., Op’T Roodt J., Stroes E.S.G., Bakker H.D., Kastelein J.J.P. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol. 2002;40(12):2117–21. doi: 10.1016/S0735-1097(02)02593-7.Kavey R.W., Manlhiot C., Runeckles K., Collins T., Gidding S.S., Demczko M., Clauss S., Harahsheh A.S., Mietus-Syder M., Khoury M., Madsen N., McCrindle B.W. Eff ectiveness and Safety of Statin Therapy in Children: A Real-World Clinical Practice Experience. CJC Open. 2020;2(6):473–82. doi: 10.1016/j.cjco.2020.06.002.Kavey R.W., Manlhiot C., Runeckles K., Collins T., Gidding S.S., Demczko M., Clauss S., Harahsheh A.S., Mietus-Syder M., Khoury M., Madsen N., McCrindle B.W. Eff ectiveness and Safety of Statin Therapy in Children: A Real-World Clinical Practice Experience. CJC Open. 2020;2(6):473–82. doi: 10.1016/j.cjco.2020.06.002.Răzvan-Valentin S., Güler S., Utkan T., Şahin T.D., Gacar G., Yazir Y., Rencber S.F., Mircea L., Cristian B., Bogdan P., Utkan N.Z. Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats. Int J Environ Res Public Health. 2022;19(4):2138. doi: 10.3390/ijerph19042138.Răzvan-Valentin S., Güler S., Utkan T., Şahin T.D., Gacar G., Yazir Y., Rencber S.F., Mircea L., Cristian B., Bogdan P., Utkan N.Z. Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats. Int J Environ Res Public Health. 2022;19(4):2138. doi: 10.3390/ijerph19042138.Cazeau R.M., Huang H., Bauer J.A., Hoff man R.P. Eff ect of Vitamins C and E on Endothelial Function in Type 1 Diabetes Mellitus. J Diabetes Res. 2016;2016:3271293. doi: 10.1155/2016/3271293.Cazeau R.M., Huang H., Bauer J.A., Hoff man R.P. Eff ect of Vitamins C and E on Endothelial Function in Type 1 Diabetes Mellitus. J Diabetes Res. 2016;2016:3271293. doi: 10.1155/2016/3271293.Bayat M., Daei S., Ziamajidi N., Abbasalipourkabir R., Nourian A. The protective eff ects of vitamins A, C, and E on zinc oxide nanoparticles (ZnO NPs)-induced liver oxidative stress in male Wistar rats. Drug Chem Toxicol. 2023;46(2):209–18. doi: 10.1080/01480545.2021.2016809.Bayat M., Daei S., Ziamajidi N., Abbasalipourkabir R., Nourian A. The protective eff ects of vitamins A, C, and E on zinc oxide nanoparticles (ZnO NPs)-induced liver oxidative stress in male Wistar rats. Drug Chem Toxicol. 2023;46(2):209–18. doi: 10.1080/01480545.2021.2016809.Jeremias A., Soodini G., Gelfand E., Xu Y., Stanton R.C., Horton E.S., Cohen D.J. Eff ects of N-acetyl-cysteine on endothelial function and infl ammation in patients with type 2 diabetes mellitus. Heart Int. 2009;4(1):e7. doi: 10.4081/hi.2009.e7.Jeremias A., Soodini G., Gelfand E., Xu Y., Stanton R.C., Horton E.S., Cohen D.J. Eff ects of N-acetyl-cysteine on endothelial function and infl ammation in patients with type 2 diabetes mellitus. Heart Int. 2009;4(1):e7. doi: 10.4081/hi.2009.e7.

The authors declare that there are no conflicts of interest present.