microcirculationРегионарное кровообращение и микроциркуляцияRegional blood circulation and microcirculation1682-66552712-9756Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1682-6655-2019-18-2-19-27microcirculation-412Research ArticleОБЗОРЫREVIEWSЭндотелиальная дисфункция: от частного к общему. Возврат к «старой парадигме»?Endothelial dysfunction: from the particular to the general. Return to the «Old Paradigm»?ВласовТ. Д.VlasovT. D.

Власов Тимур Дмитриевич – д-р мед. наук, профессор, зав. кафедрой патофизиологии с курсом клинической патофизиологии

Vlasov Timur D. – Advanced Doctor in Medical Sciences, professor, head of the Department of Pathophysiology with a course of clinical pathophysiology

tvlasov@yandex.ruНестеровичИ. И.NesterovichI. I.

Нестерович Ирина Ивановна – д-р мед. наук, профессор кафедры терапии госпитальной с курсом аллергологии и иммунологии им. акад. М. В. Черноруцкого с клиникой

Nesterovich Irina I. – Advanced Doctor in Medical Sciences, professor of the Department of Hospital Therapy with a course of Allergology and Immunology named after acad. M. V. Chernorutsky with a clinic

nester788@gmail.comШиманьскиД. А.ShimanskiD. A.

Шиманьски Даниэль Анджеевич – клинический ординатор кафедры терапии госпитальной с курсом аллергологии и иммунологии им. акад. М. В. Черноруцкого с клиникой

Shimanski Daniel A. – clinical resident of the Department of Hospital Therapy with a course of Allergology and Immunology named after acad. M. V. Chernorutsky with a clinic

next184@list.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian Federation2019110720191821927Copyright © Власов Т.Д., Нестерович И.И., Шиманьски Д.А., 20192019Власов Т.Д., Нестерович И.И., Шиманьски Д.А.Vlasov T.D., Nesterovich I.I., Shimanski D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.microcirc.ru/jour/article/view/412

Сосудистый эндотелий представляет собой гетерогенную структуру, обладающую многообразными функциями, являясь активной метаболической системой. Эндотелиальные клетки опосредуют воспалительные и иммунные процессы, регулируют адгезию лейкоцитов, проницаемость и тонус сосудов, участвуют в системе гемостаза, стимулируют процессы ангиогенеза. Дисфункция эндотелия может инициировать отдельные нарушения, но чаще является универсальным звеном в патогенезе многих заболеваний. В настоящее время эндотелиальная дисфункция представляется как дисбаланс между продукцией вазодилатирующих, ангиопротективных, антипролиферативных факторов, с одной стороны, и вазоконстриктивных, протромботических, пролиферативных факторов – с другой стороны. Проявления дисфункции эндотелия, направленность и выраженность этих изменений могут различаться в зависимости от заболевания. В обзоре приведены примеры комбинированных нарушений эндотелия при наиболее изученных и распространенных заболеваниях (эссенциальной артериальной гипертензии, сахарном диабете II типа, системных заболеваниях соединительной ткани, атеросклерозе и злокачественных новообразованиях). Несмотря на наличие редких случаев изолированной эндотелиальной дисфункции, можно утверждать, что при абсолютном большинстве заболеваний дисфункция эндотелия носит комбинированный характер. Выделение индивидуальных спектров нарушения эндотелия, типичных для конкретного заболевания, проблематично в связи с универсальностью и неспецифичностью проявлений дисфункции эндотелия. Эти выводы позволяют нам вернуться к истокам проблемы, рассматривая эндотелиальную дисфункцию как целостное понятие, не ограничиваясь определенным спектром его нарушений.

The vascular endothelium is a heterogeneous structure with diverse functions, being an active metabolic system. Endothelial cells mediate inflammatory and immune processes, regulate leukocyte adhesion, permeability and vascular tone, participate in the hemostasis system, stimulate the processes of angiogenesis. Endothelial dysfunction can initiate individual disorders, but more often it is a universal link in the pathogenesis of many diseases. Currently, endothelial dysfunction is presented as an imbalance between the production of vasodilating, angioprotective, antiproliferative factors, on the one hand, and vasoconstrictive, prothrombotic, proliferative factors, on the other hand. The manifestations of endothelial dysfunction, the direction and severity of these changes may vary depending on the disease. The review provides examples of combined endothelial disorders in the most studied and common diseases (essential hypertension, type 2 diabetes, systemic diseases of the connective tissue, atherosclerosis, and malignant tumors). Despite the presence of rare cases of isolated endothelial dysfunction, it can be argued that in the absolute majority of diseases, endothelial dysfunction has combined type of violations. The allocation of individual endothelial disorder spectra, typical for a specific disease, is problematic, due to the universality and nonspecificity of the manifestations of endothelial dysfunction. These conclusions allow us to return to the origins of this problem, considering endothelial dysfunction as a holistic concept, not limited to a certain range of its disorders.

эндотелийдисфункциямикроциркуляцияendotheliumdysfunctionmicrocirculationReferencesРодионов Ю. Я. Эндотелий как интегратор биофизических и нейрогуморальных сигналов, участвующих в регуляции сосудистого тонуса. Дисфункция эндотелия: экспериментальные и клинические исследования: Материалы IX Международ. науч.-практ. конф. Витебск, 27 мая 2016 г. / Вит. гос. мед. ун-т; редкол.: Лазуко С. С. (гл. ред.) [и др.]. – Витебск: ВГМУ, 2016. – С. 214–222. [Rodionov IuIa. Endothelium as an integrator of biophysical and neurohumoral signals involved in the regulation of vascular tone. Endothelial dysfunction: experimental and clinical studies: materials of the IX International Scientific and Practical Conference, Vitebsk, May 27, 2016. Vitebsk State Medical University; Editorial .: Lazuko SS (ch. Ed.) et al. Vitebsk, VSMU, 2016:214–222. (In Russ.)].Родионов Ю. Я. Эндотелий как интегратор биофизических и нейрогуморальных сигналов, участвующих в регуляции сосудистого тонуса. Дисфункция эндотелия: экспериментальные и клинические исследования: Материалы IX Международ. науч.-практ. конф. Витебск, 27 мая 2016 г. / Вит. гос. мед. ун-т; редкол.: Лазуко С. С. (гл. ред.) [и др.]. – Витебск: ВГМУ, 2016. – С. 214–222. [Rodionov IuIa. Endothelium as an integrator of biophysical and neurohumoral signals involved in the regulation of vascular tone. Endothelial dysfunction: experimental and clinical studies: materials of the IX International Scientific and Practical Conference, Vitebsk, May 27, 2016. Vitebsk State Medical University; Editorial .: Lazuko SS (ch. Ed.) et al. Vitebsk, VSMU, 2016:214–222. (In Russ.)].Эндотелий – структурная основа системы кровообращения: история проблемы / Ю. Л. Шевченко, П. Е. Асташев, С. А. Матвеев, В. Г. Гудымович // Вестн. Нац. медико-хирург. Центра им. Н. И. Пирогова. – 2011. – Т. 6, № 2. – С. 9–15. [Shevchenko JuL, Astashev PE, Matveev SA, Goodymovich VG. Endothelium – structural basis of circulatory system: the history of the problem. Bulletin of Pirogov National Medical and Surgical Center. 2011;6(2):9– 15. (In Russ.)].Эндотелий – структурная основа системы кровообращения: история проблемы / Ю. Л. Шевченко, П. Е. Асташев, С. А. Матвеев, В. Г. Гудымович // Вестн. Нац. медико-хирург. Центра им. Н. И. Пирогова. – 2011. – Т. 6, № 2. – С. 9–15. [Shevchenko JuL, Astashev PE, Matveev SA, Goodymovich VG. Endothelium – structural basis of circulatory system: the history of the problem. Bulletin of Pirogov National Medical and Surgical Center. 2011;6(2):9– 15. (In Russ.)].Yukihito Higashi. Assessment of Endothelial Function History, Methodological Aspects, and Clinical Perspectives. Int Heart J. 2015;56(2):125–134. Doi:10.1536/ihj.14-385.Yukihito Higashi. Assessment of Endothelial Function History, Methodological Aspects, and Clinical Perspectives. Int Heart J. 2015;56(2):125–134. Doi:10.1536/ihj.14-385.Васина Л. В., Власов Т. Д., Петрищев Н. Н. Функциональная гетерогенность эндотелия (обзор) // Артериальная гипертензия. – 2017. – Т. 23, № 2. – С. 88– 102. [Vasina LV, Vlasov TD, Petrishchev NN. Functional heterogeneity of the endothelium (the review). Arterial’naya Gipertenziya. (Arterial Hypertension). 2017;23(2):88–102. (In Russ.)]. Doi: 10.18705/1607-419X-2017-23-2-88-102.Васина Л. В., Власов Т. Д., Петрищев Н. Н. Функциональная гетерогенность эндотелия (обзор) // Артериальная гипертензия. – 2017. – Т. 23, № 2. – С. 88– 102. [Vasina LV, Vlasov TD, Petrishchev NN. Functional heterogeneity of the endothelium (the review). Arterial’naya Gipertenziya. (Arterial Hypertension). 2017;23(2):88–102. (In Russ.)]. Doi: 10.18705/1607-419X-2017-23-2-88-102.Мельникова Ю. С., Макарова Т. П. Эндотелиальная дисфункция как центральное звено патогенеза хронических болезней // Казан. мед. журн. – 2015. – Т. 96, № 4. – C. 659–665. [Mel’nikova JuS, Makarova TP. Endothelial dysfunction as the key link of chronic diseases pathogenesis. Kazan Medical Journal. 2015;96(4):659–665. (In Russ.)]. Doi: 10.17750/KMJ2015-659.Мельникова Ю. С., Макарова Т. П. Эндотелиальная дисфункция как центральное звено патогенеза хронических болезней // Казан. мед. журн. – 2015. – Т. 96, № 4. – C. 659–665. [Mel’nikova JuS, Makarova TP. Endothelial dysfunction as the key link of chronic diseases pathogenesis. Kazan Medical Journal. 2015;96(4):659–665. (In Russ.)]. Doi: 10.17750/KMJ2015-659.Васина Л. В., Петрищев Н. Н., Власов Т. Д. Эндотелиальная дисфункция и ее основные маркеры // Регионарное кровообращение и микроциркуляция. – 2017. – Т. 16, № 1. – С. 4–15. [Vasina LV, Petrishchev NN, Vlasov TD. Markers of endothelial dysfunction. Regional blood circulation and microcirculation. 2017;16(1):4–15. (In Russ.)]. Doi:10.24884/1682-6655-2017-16-1-4-15.Васина Л. В., Петрищев Н. Н., Власов Т. Д. Эндотелиальная дисфункция и ее основные маркеры // Регионарное кровообращение и микроциркуляция. – 2017. – Т. 16, № 1. – С. 4–15. [Vasina LV, Petrishchev NN, Vlasov TD. Markers of endothelial dysfunction. Regional blood circulation and microcirculation. 2017;16(1):4–15. (In Russ.)]. Doi:10.24884/1682-6655-2017-16-1-4-15.Klinger JR, Kadowitz PJ. The Nitric Oxide Pathway in Pulmonary Vascular Disease. Am J Cardiol. 2017. Oct 15;120(8S):S71–S79. Doi:10.1016/j.amjcard.2017.06.012.Klinger JR, Kadowitz PJ. The Nitric Oxide Pathway in Pulmonary Vascular Disease. Am J Cardiol. 2017. Oct 15;120(8S):S71–S79. Doi:10.1016/j.amjcard.2017.06.012.Leineweber K, Moosmang S, Paulson D. Genetics of NO Deficiency. Am J Cardiol. 2017. Oct 15;120(8S):S80–S88. Doi:10.1016/j.amjcard.2017.06.013. 11. Randi AM. Endothelial dysfunction in von Willebrand disease: angiogenesis and angiodysplasia. Thromb Res. 2016; 141(Suppl. 2):S55–S58. Doi:10.1016/s0049-3848(16) 30366-8.Leineweber K, Moosmang S, Paulson D. Genetics of NO Deficiency. Am J Cardiol. 2017. Oct 15;120(8S):S80–S88. Doi:10.1016/j.amjcard.2017.06.013. 11. Randi AM. Endothelial dysfunction in von Willebrand disease: angiogenesis and angiodysplasia. Thromb Res. 2016; 141(Suppl. 2):S55–S58. Doi:10.1016/s0049-3848(16) 30366-8.Echahdi H, El Hasbaoui B, El Khorassani M, Agadr A, Khattab M. Von Willebrand’s disease: case report and review of literature. Pan Afr Med J. 2017. Jun 29;27:147. Doi: 10.11604/ pamj.2017.27.147.12248.Echahdi H, El Hasbaoui B, El Khorassani M, Agadr A, Khattab M. Von Willebrand’s disease: case report and review of literature. Pan Afr Med J. 2017. Jun 29;27:147. Doi: 10.11604/ pamj.2017.27.147.12248.Kandasamy Y, Hartley L, Rudd D, Smith R. The association between systemic vascular endothelial growth factor and retinopathy of prematurity in premature infants: a systematic review. Br J Ophthalmol. 2017. Jan;101(1):21–24. Doi: 10.1136/bjophthalmol-2016-308828.Kandasamy Y, Hartley L, Rudd D, Smith R. The association between systemic vascular endothelial growth factor and retinopathy of prematurity in premature infants: a systematic review. Br J Ophthalmol. 2017. Jan;101(1):21–24. Doi: 10.1136/bjophthalmol-2016-308828.Bernatova I. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence? BioMed Research International. 2014;(2014):1–14. Doi: 10.1155/2014/598271.Bernatova I. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence? BioMed Research International. 2014;(2014):1–14. Doi: 10.1155/2014/598271.Assis AM, Costa FF, Arruda VR, Annichino-Bizzacchi JM, Bertuzzo CS. Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients. J Hum Genet. 2007;52(3):237–243. Doi: 10.1007/s10038-006-0104-3.Assis AM, Costa FF, Arruda VR, Annichino-Bizzacchi JM, Bertuzzo CS. Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients. J Hum Genet. 2007;52(3):237–243. Doi: 10.1007/s10038-006-0104-3.Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascón GA, Hernandez G, Murray P, De Backer D; ADQI XIV Workgroup. The endothelium in sepsis. Shock. 2016;45(3): 259–270. Doi: 10.1097/SHK.0000000000000473.Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascón GA, Hernandez G, Murray P, De Backer D; ADQI XIV Workgroup. The endothelium in sepsis. Shock. 2016;45(3): 259–270. Doi: 10.1097/SHK.0000000000000473.DeLisser HM, Christofidou-Solomidou M, Sun J, Nakada MT, Sullivan KE. Loss of endothelial surface expression of E-selectin in a patient with recurrent infections. Blood. 1999; 94(3):884–894.DeLisser HM, Christofidou-Solomidou M, Sun J, Nakada MT, Sullivan KE. Loss of endothelial surface expression of E-selectin in a patient with recurrent infections. Blood. 1999; 94(3):884–894.Cho SH, Jeong MH, Park IH, Choi JS, Yoon HJ, Kim KH, Hong YJ, Park HW, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC. Endothelial dysfunction, increased carotid artery intimamedia thickness and pulse wave velocity, and increased level of inflammatory markers are associated with variant angina. J Cardiol. 2009;54(2):183–191. Doi: 10.1016/j.jjcc.2009.05.003.Cho SH, Jeong MH, Park IH, Choi JS, Yoon HJ, Kim KH, Hong YJ, Park HW, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC. Endothelial dysfunction, increased carotid artery intimamedia thickness and pulse wave velocity, and increased level of inflammatory markers are associated with variant angina. J Cardiol. 2009;54(2):183–191. Doi: 10.1016/j.jjcc.2009.05.003.Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002;4(6):465–473. Doi: 10.1038/sj.neo. 7900263.Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002;4(6):465–473. Doi: 10.1038/sj.neo. 7900263.Bellamy MF, Goodfellow J, Tweddel AC, Dunstan FD, Lewis MJ, Henderson AH. Syndrome X and endothelial dysfunction. Cardiovasc Res. 1998;40(2):410–417. Doi: 10. 1016/s0008-6363(98)00184-9.Bellamy MF, Goodfellow J, Tweddel AC, Dunstan FD, Lewis MJ, Henderson AH. Syndrome X and endothelial dysfunction. Cardiovasc Res. 1998;40(2):410–417. Doi: 10. 1016/s0008-6363(98)00184-9.Temprano KK. A Review of Raynaud’s Disease. Mo Med. 2016;113(2):123–126.Temprano KK. A Review of Raynaud’s Disease. Mo Med. 2016;113(2):123–126.Baszczuk A, Kopczyński Z, Thielemann A. Endothelial dysfunction in patients with primary hypertension and hyperhomocysteinemia. Postepy Hig Med Dosw (online), 2014; (68):91–100. Doi: 10.5604/17322693.1087521.Baszczuk A, Kopczyński Z, Thielemann A. Endothelial dysfunction in patients with primary hypertension and hyperhomocysteinemia. Postepy Hig Med Dosw (online), 2014; (68):91–100. Doi: 10.5604/17322693.1087521.Dharmashankar K, Widlansky ME. Vascular Endothelial Function and Hypertension: Insights and Directions. Curr Hypertens Rep. 2010;12(6):448–455. Doi: 10.1007/s11906- 010-0150-2.Dharmashankar K, Widlansky ME. Vascular Endothelial Function and Hypertension: Insights and Directions. Curr Hypertens Rep. 2010;12(6):448–455. Doi: 10.1007/s11906- 010-0150-2.Giles T D, Sander GE, Nossaman BD, Kadowitz PJ. Impaired Vasodilation in the Pathogenesis of Hypertension: Focus on Nitric Oxide, Endothelial-Derived Hyperpolarizing Factors, and Prostaglandins. The Journal of Clinical Hypertension. 2012;14(4):198–205. Doi: 10.1111/j.1751-7176. 2012.00606.x.Giles T D, Sander GE, Nossaman BD, Kadowitz PJ. Impaired Vasodilation in the Pathogenesis of Hypertension: Focus on Nitric Oxide, Endothelial-Derived Hyperpolarizing Factors, and Prostaglandins. The Journal of Clinical Hypertension. 2012;14(4):198–205. Doi: 10.1111/j.1751-7176. 2012.00606.x.Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. British Journal of Pharmacology. 2009;157(4):527–536. Doi: 10.1111/j.1476-5381. 2009.00240.x.Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. British Journal of Pharmacology. 2009;157(4):527–536. Doi: 10.1111/j.1476-5381. 2009.00240.x.Bleakley C, Hamilton PK, Pumb R, Harbinson M, McVeigh GE. Endothelial Function in Hypertension: Victim or Culprit? The Journal of Clinical Hypertension (Greenwich). 2015;17(8):651–654. Doi: 10.1111/jch.12546.Bleakley C, Hamilton PK, Pumb R, Harbinson M, McVeigh GE. Endothelial Function in Hypertension: Victim or Culprit? The Journal of Clinical Hypertension (Greenwich). 2015;17(8):651–654. Doi: 10.1111/jch.12546.De Faria AP, Ritter AM V, Sabbatini AR, Corrêa NB, Brunelli V, Modolo R, Moreno H. Deregulation of Soluble Adhesion Molecules in Resistant Hypertension and Its Role in Cardiovascular Remodeling. Circulation Journal. 2016; 80(5):1196–1201. Doi:10.1253/circj.cj-16-0058.De Faria AP, Ritter AM V, Sabbatini AR, Corrêa NB, Brunelli V, Modolo R, Moreno H. Deregulation of Soluble Adhesion Molecules in Resistant Hypertension and Its Role in Cardiovascular Remodeling. Circulation Journal. 2016; 80(5):1196–1201. Doi:10.1253/circj.cj-16-0058.Tadzic R, Mihalj M, Vcev A, Ennen J, Tadzic A, Drenjancevic I. The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy. Kidney Blood Press Res. 2013;37:103–115. Doi: 10.1159/000350064.Tadzic R, Mihalj M, Vcev A, Ennen J, Tadzic A, Drenjancevic I. The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy. Kidney Blood Press Res. 2013;37:103–115. Doi: 10.1159/000350064.Madej A, Okopień B, Kowalski J, Haberka M, Herman ZS. Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension. Pharmacol. Rep. 2005;57(6):878–881.Madej A, Okopień B, Kowalski J, Haberka M, Herman ZS. Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension. Pharmacol. Rep. 2005;57(6):878–881.Hlubocka Z, Umnerova V, Heller S, Peleska J, Jindra A, Jachymova M, Kvasnicka J, Horky K, Aschermann M. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. Journal of Human Hypertension. 2002;(16):557–562. Doi: 10.1038/sj.jhh.1001403.Hlubocka Z, Umnerova V, Heller S, Peleska J, Jindra A, Jachymova M, Kvasnicka J, Horky K, Aschermann M. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. Journal of Human Hypertension. 2002;(16):557–562. Doi: 10.1038/sj.jhh.1001403.Małyszko J, Tymcio J. Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with essential arterial hypertension. Pol Arch Med Wewn. 2008;118(1–2):36–41. Doi: 10.20452/pamw.300. 32. Khaleghi M, Singletary LA, Kondragunta V, Bailey KR, Turner ST, Mosley TH Jr, Kullo IJ. Haemostatic markers are associated with measures of vascular disease in adults with hypertension. J Hum Hypertens. 2009;23(8):530–537. Doi: 10.1038/jhh.2008.170.Małyszko J, Tymcio J. Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with essential arterial hypertension. Pol Arch Med Wewn. 2008;118(1–2):36–41. Doi: 10.20452/pamw.300. 32. Khaleghi M, Singletary LA, Kondragunta V, Bailey KR, Turner ST, Mosley TH Jr, Kullo IJ. Haemostatic markers are associated with measures of vascular disease in adults with hypertension. J Hum Hypertens. 2009;23(8):530–537. Doi: 10.1038/jhh.2008.170.Makris T, Stavroulakis G, Papadopoulos D, Paizis I, Krespi P, Tsoukala C, Hatzizacharias A, Votteas V. White coat hypertension and haemostatic/fibrinolytic balance disorders. Eur. Cytokine Netw. 2006;17(2):137–141.Makris T, Stavroulakis G, Papadopoulos D, Paizis I, Krespi P, Tsoukala C, Hatzizacharias A, Votteas V. White coat hypertension and haemostatic/fibrinolytic balance disorders. Eur. Cytokine Netw. 2006;17(2):137–141.Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J, Beckman JA, Harrison DG, Moslehi J. Mechanisms of VEGF-Inhibitor Associated Hypertension and Vascular Disease. Hypertension. 2018;71(2):e1–e8. Doi:10.1161/ hypertensionaha.117.10271.Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J, Beckman JA, Harrison DG, Moslehi J. Mechanisms of VEGF-Inhibitor Associated Hypertension and Vascular Disease. Hypertension. 2018;71(2):e1–e8. Doi:10.1161/ hypertensionaha.117.10271.Marek-Trzonkowska N, Kwieczyńska A, Reiwer-Gostomska M, Koliński T, Molisz A, Siebert J. Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus AntiAngiogenic Factors. PLoS One. 2015;10(5):e0126190. Doi: 10.1371/journal.pone.0126190.Marek-Trzonkowska N, Kwieczyńska A, Reiwer-Gostomska M, Koliński T, Molisz A, Siebert J. Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus AntiAngiogenic Factors. PLoS One. 2015;10(5):e0126190. Doi: 10.1371/journal.pone.0126190.Collins T, Gray K, Bista M, Skinner M, Hardy C, Wang H, Mettetal JT, Harmer AR. Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension. Br J Pharmacol. 2018; 175(4):618–630. Doi: 10.1111/bph.14103.Collins T, Gray K, Bista M, Skinner M, Hardy C, Wang H, Mettetal JT, Harmer AR. Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension. Br J Pharmacol. 2018; 175(4):618–630. Doi: 10.1111/bph.14103.Hamnvik OP, Choueiri TK, Turchin A, McKay RR, Goyal L, Davis M, Kaymakcalan MD, Williams JS. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer. 2015;121(2):311–319. Doi: 10.1002/cncr.28972.Hamnvik OP, Choueiri TK, Turchin A, McKay RR, Goyal L, Davis M, Kaymakcalan MD, Williams JS. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer. 2015;121(2):311–319. Doi: 10.1002/cncr.28972.Robinson ES, Khankin EV, Karumanchi SA, Humphreys BD. Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol, 2010;30(6):591– 601. Doi: 10.1016/j.semnephrol.2010.09.007.Robinson ES, Khankin EV, Karumanchi SA, Humphreys BD. Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol, 2010;30(6):591– 601. Doi: 10.1016/j.semnephrol.2010.09.007.Curwen JO, Musgrove HL, Kendrew J, Richmond GH, Ogilvie DJ, Wedge SR. Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy. Clin Cancer Res, 2008;14(10):3124–3131. Doi: 10. 1158/1078-0432.CCR-07-4783.Curwen JO, Musgrove HL, Kendrew J, Richmond GH, Ogilvie DJ, Wedge SR. Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy. Clin Cancer Res, 2008;14(10):3124–3131. Doi: 10. 1158/1078-0432.CCR-07-4783.Torimoto K, Okada Y, Tanaka Y. [Type 2 Diabetes and Vascular Endothelial Dysfunction]. [Article in Japanese]. J UOEH, 2018;40(1):65–75. Doi: 10.7888/juoeh.40.65.Torimoto K, Okada Y, Tanaka Y. [Type 2 Diabetes and Vascular Endothelial Dysfunction]. [Article in Japanese]. J UOEH, 2018;40(1):65–75. Doi: 10.7888/juoeh.40.65.Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol, 2018;17(1):121. Doi: 10.1186/s12933-018-0763-3.Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol, 2018;17(1):121. Doi: 10.1186/s12933-018-0763-3.Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. 2013;10(6):472–482. Doi: 10.1177/1479164113500680.Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. 2013;10(6):472–482. Doi: 10.1177/1479164113500680.Meigs JB, O’donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, Nathan DM, Sullivan LM, D’Agostino RB, Wilson PW. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. Diabetes, 2006;55(2):530–537. Doi: 10.2337/diabetes. 55.02.06.db05-1041.Meigs JB, O’donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, Nathan DM, Sullivan LM, D’Agostino RB, Wilson PW. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. Diabetes, 2006;55(2):530–537. Doi: 10.2337/diabetes. 55.02.06.db05-1041.Zhang H, Dellsperger KC, Zhang C. The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Basic Res Cardiol. 2012;107(1):237. Doi: 10.1007/s00395-011-0237-1.Zhang H, Dellsperger KC, Zhang C. The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Basic Res Cardiol. 2012;107(1):237. Doi: 10.1007/s00395-011-0237-1.Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O’Neal DN, Januszewski AS. Biomarkers in Diabetic Retinopathy. Rev Diabet Stud, 2015;12(1–2):159–195. Doi: 10.1900/ RDS.2015.12.159.Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O’Neal DN, Januszewski AS. Biomarkers in Diabetic Retinopathy. Rev Diabet Stud, 2015;12(1–2):159–195. Doi: 10.1900/ RDS.2015.12.159.Jerić M, Vukojević K, Vuica A, Filipović N. Diabetes mellitus influences the expression of NPY and VEGF in neurons of rat trigeminal ganglion. Neuropeptides. 2017;(62):57–64. Doi: 10.1016/j.npep.2016.11.001.Jerić M, Vukojević K, Vuica A, Filipović N. Diabetes mellitus influences the expression of NPY and VEGF in neurons of rat trigeminal ganglion. Neuropeptides. 2017;(62):57–64. Doi: 10.1016/j.npep.2016.11.001.Hang H, Yuan S, Yang Q, Yuan D, Liu Q. Multiplex bead array assay of plasma cytokines in type 2 diabetes mellitus with diabetic retinopathy. Mol Vis. 2014;(20):1137–1145.Hang H, Yuan S, Yang Q, Yuan D, Liu Q. Multiplex bead array assay of plasma cytokines in type 2 diabetes mellitus with diabetic retinopathy. Mol Vis. 2014;(20):1137–1145.Вклад дисфункции эндотелия в повреждение центральной нервной системы при сахарном диабете 2 типа / А. В. Симаненкова, М. Н. Макарова, Л. В. Васина, Т. Д. Власов // Смолен. мед. альм. – 2018. – № 4. – С. 195– 197. [Simanenkova AV, Makarova MN, Vasina LV, Vlasov TD. Contribution of endothelial dysfunction to central nervous system damage in type 2 diabetes mellitus. Smolensk Medical Almona. 2018;(4):195–197. (In Russ.)].Вклад дисфункции эндотелия в повреждение центральной нервной системы при сахарном диабете 2 типа / А. В. Симаненкова, М. Н. Макарова, Л. В. Васина, Т. Д. Власов // Смолен. мед. альм. – 2018. – № 4. – С. 195– 197. [Simanenkova AV, Makarova MN, Vasina LV, Vlasov TD. Contribution of endothelial dysfunction to central nervous system damage in type 2 diabetes mellitus. Smolensk Medical Almona. 2018;(4):195–197. (In Russ.)].Atehortúa L, Rojas M, Vásquez GM, Castaño D. Endothelial Alterations in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Potential Effect of Monocyte Interaction. Mediators Inflamm. 2017;2017:9680729. Doi: 10.1155/2017/9680729.Atehortúa L, Rojas M, Vásquez GM, Castaño D. Endothelial Alterations in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Potential Effect of Monocyte Interaction. Mediators Inflamm. 2017;2017:9680729. Doi: 10.1155/2017/9680729.Nagy G, Koncz A, Telarico T, Fernandez D, Ersek B, Buzás E, Perl A. Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther. 2010;12(3):210. Doi: 10.1186/ar3045.Nagy G, Koncz A, Telarico T, Fernandez D, Ersek B, Buzás E, Perl A. Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther. 2010;12(3):210. Doi: 10.1186/ar3045.Liu J, Wang X, Yang X, Yan Q, Wang S, Han W. Investigating the role of angiogenesis in systemic lupus erythematosus. Lupus, 2015;24(6):621–627. Doi: 10.1177/ 0961203314556293.Liu J, Wang X, Yang X, Yan Q, Wang S, Han W. Investigating the role of angiogenesis in systemic lupus erythematosus. Lupus, 2015;24(6):621–627. Doi: 10.1177/ 0961203314556293.Bărbulescu AL, Vreju AF, Bugă AM, Sandu RE, Criveanu C, Tudoraşcu DR, Gheonea IA, Ciurea PL. Vascular endothelial growth factor in systemic lupus erythematosus – correlations with disease activity and nailfold capillaroscopy changes. Rom J Morphol Embryol. 2015; 56(3):1011–1016.Bărbulescu AL, Vreju AF, Bugă AM, Sandu RE, Criveanu C, Tudoraşcu DR, Gheonea IA, Ciurea PL. Vascular endothelial growth factor in systemic lupus erythematosus – correlations with disease activity and nailfold capillaroscopy changes. Rom J Morphol Embryol. 2015; 56(3):1011–1016.Zhou L, Lu G, Shen L, Wang L, Wang M. Serum levels of three angiogenic factors in systemic lupus erythematosus and their clinical significance. Biomed Res Int. 2014;2014:627126. Doi: 10.1155/2014/627126.Zhou L, Lu G, Shen L, Wang L, Wang M. Serum levels of three angiogenic factors in systemic lupus erythematosus and their clinical significance. Biomed Res Int. 2014;2014:627126. Doi: 10.1155/2014/627126.Buie JJ, Renaud LL, Muise-Helmericks R, Oates JC. IFN-α Negatively Regulates the Expression of Endothelial Nitric Oxide Synthase and Nitric Oxide Production: Implications for Systemic Lupus Erythematosus. J Immunol. 2017;199(6):1979–1988. Doi: 10.4049/jimmunol. 1600108.Buie JJ, Renaud LL, Muise-Helmericks R, Oates JC. IFN-α Negatively Regulates the Expression of Endothelial Nitric Oxide Synthase and Nitric Oxide Production: Implications for Systemic Lupus Erythematosus. J Immunol. 2017;199(6):1979–1988. Doi: 10.4049/jimmunol. 1600108.Singh S, Wu T, Xie C, Vanarsa K, Han J, Mahajan T, Oei HB, Ahn C, Zhou XJ, Putterman C, Saxena R, Mohan C. Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther. 2012;14(4):R164. Doi: 10.1186/ar3912.Singh S, Wu T, Xie C, Vanarsa K, Han J, Mahajan T, Oei HB, Ahn C, Zhou XJ, Putterman C, Saxena R, Mohan C. Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther. 2012;14(4):R164. Doi: 10.1186/ar3912.Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620–636. Doi: 10.1161/circresaha. 115.306301.Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620–636. Doi: 10.1161/circresaha. 115.306301.Liu X, Ma D, Zheng S, Zha K, Feng J, Cai Y, Jiang F, Li J, Fan Z. The roles of nitric oxide and hydrogen sulfide in the anti-atherosclerotic effect of atorvastatin. J Cardiovasc Med (Hagerstown), 2015;16(1):22–28. Doi: 10.2459/ JCM.0000000000000012.Liu X, Ma D, Zheng S, Zha K, Feng J, Cai Y, Jiang F, Li J, Fan Z. The roles of nitric oxide and hydrogen sulfide in the anti-atherosclerotic effect of atorvastatin. J Cardiovasc Med (Hagerstown), 2015;16(1):22–28. Doi: 10.2459/ JCM.0000000000000012.Jönsson Rylander AC, Lindgren A, Deinum J, Bergström GM, Böttcher G, Kalies I, Wåhlander K. Fibrinolysis inhibitors in plaque stability: a morphological association of PAI-1 and TAFI in advanced carotid plaque. J Thromb Haemost, 2017;15(4):758–769. Doi: 10.1111/jth.13641.Jönsson Rylander AC, Lindgren A, Deinum J, Bergström GM, Böttcher G, Kalies I, Wåhlander K. Fibrinolysis inhibitors in plaque stability: a morphological association of PAI-1 and TAFI in advanced carotid plaque. J Thromb Haemost, 2017;15(4):758–769. Doi: 10.1111/jth.13641.Montoro-García S, Shantsila E, Lip GY. Potential value of targeting von Willebrand factor in atherosclerotic cardiovascular disease. Expert Opin Ther Targets. 2014; 18(1):43–53. Doi: 10.1517/14728222.2013.840585.Montoro-García S, Shantsila E, Lip GY. Potential value of targeting von Willebrand factor in atherosclerotic cardiovascular disease. Expert Opin Ther Targets. 2014; 18(1):43–53. Doi: 10.1517/14728222.2013.840585.Tatsumi K, Mackman N. Tissue Factor and Atherothrombosis. J Atheroscler Thromb. 2015;22(6):543–549. Doi: 10.5551/jat.30940.Tatsumi K, Mackman N. Tissue Factor and Atherothrombosis. J Atheroscler Thromb. 2015;22(6):543–549. Doi: 10.5551/jat.30940.Marzolla V, Armani A, Mammi C, Moss ME, Pagliarini V, Pontecorvo L, Antelmi A, Fabbri A, Rosano G, Jaffe IZ, Caprio M. Essential role of ICAM-1 in aldosterone-induced atherosclerosis. Int J Cardiol. 2017;(232):233–242. Doi: 10. 1016/j.ijcard.2017.01.013.Marzolla V, Armani A, Mammi C, Moss ME, Pagliarini V, Pontecorvo L, Antelmi A, Fabbri A, Rosano G, Jaffe IZ, Caprio M. Essential role of ICAM-1 in aldosterone-induced atherosclerosis. Int J Cardiol. 2017;(232):233–242. Doi: 10. 1016/j.ijcard.2017.01.013.Ma S, Tian XY, Zhang Y, Mu C, Shen H, Bismuth J, Pownall HJ, Huang Y, Wong WT. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep. 2016;(6):22910. Doi: 10.1038/srep22910.Ma S, Tian XY, Zhang Y, Mu C, Shen H, Bismuth J, Pownall HJ, Huang Y, Wong WT. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep. 2016;(6):22910. Doi: 10.1038/srep22910.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.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.Dumanskiy YV, Stoliarova OY, Syniachenko OV, Iegudina ED. Endothelial dysfunction of vessels at lung cancer. Exp Oncol. 2015;37(4):277–280. Doi: 10.31768/2312-8852. 2015.37(4):277-280.Dumanskiy YV, Stoliarova OY, Syniachenko OV, Iegudina ED. Endothelial dysfunction of vessels at lung cancer. Exp Oncol. 2015;37(4):277–280. Doi: 10.31768/2312-8852. 2015.37(4):277-280.Pacia MZ, Buczek E, Blazejczyk A, Gregorius A, Wietrzyk J, Chlopicki S, Baranska M, Kaczor A. 3D Raman imaging of systemic endothelial dysfunction in the murine model of metastatic breast cancer. Anal Bioanal Chem, 2016; 408(13):3381–3387. Doi: 10.1007/s00216-016-9436-9.Pacia MZ, Buczek E, Blazejczyk A, Gregorius A, Wietrzyk J, Chlopicki S, Baranska M, Kaczor A. 3D Raman imaging of systemic endothelial dysfunction in the murine model of metastatic breast cancer. Anal Bioanal Chem, 2016; 408(13):3381–3387. Doi: 10.1007/s00216-016-9436-9.Salimian Rizi B, Achreja A, Nagrath D. Nitric Oxide: The Forgotten Child of Tumor Metabolism. Trends Cancer, 2017;3(9):659–672. Doi: 10.1016/j.trecan.2017.07.005.Salimian Rizi B, Achreja A, Nagrath D. Nitric Oxide: The Forgotten Child of Tumor Metabolism. Trends Cancer, 2017;3(9):659–672. Doi: 10.1016/j.trecan.2017.07.005.Vaiou M, Pangou E, Liakos P, Sakellaridis N, Vassilopoulos G, Dimas K, Papandreou C. Endothelin-1 (ET-1) induces resistance to bortezomib in human multiple myeloma cells via a pathway involving the ETB receptor and upregulation of proteasomal activity. J Cancer Res Clin Oncol. 2016;142(10):2141–2158. Doi: 10.1007/s00432-016-2216-2.Vaiou M, Pangou E, Liakos P, Sakellaridis N, Vassilopoulos G, Dimas K, Papandreou C. Endothelin-1 (ET-1) induces resistance to bortezomib in human multiple myeloma cells via a pathway involving the ETB receptor and upregulation of proteasomal activity. J Cancer Res Clin Oncol. 2016;142(10):2141–2158. Doi: 10.1007/s00432-016-2216-2.O’Sullivan JM, Preston RJS, Robson T, O’Donnell JS. Emerging Roles for von Willebrand Factor in Cancer Cell Biology. Semin Thromb Hemost. 2018;44(2):159–166. Doi: 10.1055/s-0037-1607352.O’Sullivan JM, Preston RJS, Robson T, O’Donnell JS. Emerging Roles for von Willebrand Factor in Cancer Cell Biology. Semin Thromb Hemost. 2018;44(2):159–166. Doi: 10.1055/s-0037-1607352.Christensen A, Kiss K, Lelkaitis G, Juhl K, Persson M, Charabi BW, Mortensen J, Forman JL, Sørensen AL, Jensen DH, Kjaer A, von Buchwald C. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer. BMC Cancer. 2017;17(1):572. Doi: 10.1186/s12885-017-3563-3.Christensen A, Kiss K, Lelkaitis G, Juhl K, Persson M, Charabi BW, Mortensen J, Forman JL, Sørensen AL, Jensen DH, Kjaer A, von Buchwald C. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer. BMC Cancer. 2017;17(1):572. Doi: 10.1186/s12885-017-3563-3.Liu WJ, Zhou L, Liang ZY, Zhou WX, You L, Zhang TP, Zhao YP. Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma. Chin Med J (Engl). 2018;131(24):2947– 2952. Doi: 10.4103/0366-6999.247211.Liu WJ, Zhou L, Liang ZY, Zhou WX, You L, Zhang TP, Zhao YP. Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma. Chin Med J (Engl). 2018;131(24):2947– 2952. Doi: 10.4103/0366-6999.247211.Takayama Y, Hattori N, Hamada H, Masuda T, Omori K, Akita S, Iwamoto H, Fujitaka K, Kohno N. Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma. Cancer Res. 2016;76(11):3285– 3294. Doi: 10.1158/0008-5472.CAN-15-1796.Takayama Y, Hattori N, Hamada H, Masuda T, Omori K, Akita S, Iwamoto H, Fujitaka K, Kohno N. Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma. Cancer Res. 2016;76(11):3285– 3294. Doi: 10.1158/0008-5472.CAN-15-1796.Kim KJ, Kwon SH, Yun JH, Jeong HS, Kim HR, Lee EH, Ye SK, Cho CH. STAT3 activation in endothelial cells is important for tumor metastasis via increased cell adhesion molecule expression. Oncogene. 2017;36(39):5445–5459. Doi: 10.1038/onc.2017.148.Kim KJ, Kwon SH, Yun JH, Jeong HS, Kim HR, Lee EH, Ye SK, Cho CH. STAT3 activation in endothelial cells is important for tumor metastasis via increased cell adhesion molecule expression. Oncogene. 2017;36(39):5445–5459. Doi: 10.1038/onc.2017.148.Abraham V, Cao G, Parambath A, Lawal F, Handumrongkul C, Debs R, DeLisser HM. Involvement of TIMP-1 in PECAM-1-mediated tumor dissemination. Int J Oncol. 2018;53(2):488–502. Doi: 10.3892/ijo.2018.4422.Abraham V, Cao G, Parambath A, Lawal F, Handumrongkul C, Debs R, DeLisser HM. Involvement of TIMP-1 in PECAM-1-mediated tumor dissemination. Int J Oncol. 2018;53(2):488–502. Doi: 10.3892/ijo.2018.4422.Zhang X, Liu C, Hu F, Zhang Y, Wang J, Gao Y, Jiang Y, Zhang Y, Lan X. PET Imaging of VCAM-1 Expression and Monitoring Therapy Response in Tumor with a 68Ga-Labeled Single Chain Variable Fragment. Mol Pharm. 2018;15(2):609– 618. Doi:10.1021/acs.molpharmaceut.7b00961.Zhang X, Liu C, Hu F, Zhang Y, Wang J, Gao Y, Jiang Y, Zhang Y, Lan X. PET Imaging of VCAM-1 Expression and Monitoring Therapy Response in Tumor with a 68Ga-Labeled Single Chain Variable Fragment. Mol Pharm. 2018;15(2):609– 618. Doi:10.1021/acs.molpharmaceut.7b00961.Siveen KS, Prabhu K, Krishnankutty R, Kuttikrishnan S, Tsakou M, Alali FQ, Dermime S, Mohammad RM, Uddin S. Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges. Curr Vasc Pharmacol. 2017;15(4):339–351. Doi: 10.2174/1570161115 666170105124038.Siveen KS, Prabhu K, Krishnankutty R, Kuttikrishnan S, Tsakou M, Alali FQ, Dermime S, Mohammad RM, Uddin S. Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges. Curr Vasc Pharmacol. 2017;15(4):339–351. Doi: 10.2174/1570161115 666170105124038.Iyer AK, Ramesh V, Castro CA, Kaushik V, Kulkarni YM, Wright CA, Venkatadri R, Rojanasakul Y, Azad N. Nitric oxide mediates bleomycin-induced angiogenesis and pulmonary fibrosis via regulation of VEGF. J Cell Biochem. 2015;116(11):2484–2493. Doi: 10.1002/jcb.25192.Iyer AK, Ramesh V, Castro CA, Kaushik V, Kulkarni YM, Wright CA, Venkatadri R, Rojanasakul Y, Azad N. Nitric oxide mediates bleomycin-induced angiogenesis and pulmonary fibrosis via regulation of VEGF. J Cell Biochem. 2015;116(11):2484–2493. Doi: 10.1002/jcb.25192.Манухина Е. Б., Малышев И. Ю. Роль оксида азота в развитии и предупреждении дисфункции эндотелия // Вест. Витеб. гос. мед. ун-та. – 2003. – Т. 2, № 2. – С. 5–17. [Manukhina EB, Malyshev I.Yu. The role of nitric oxide in the development and prevention of endothelial dysfunction. Bulletin of Vitebsk State Medical University. 2003;2(2):5–17. (In Russ.)].Манухина Е. Б., Малышев И. Ю. Роль оксида азота в развитии и предупреждении дисфункции эндотелия // Вест. Витеб. гос. мед. ун-та. – 2003. – Т. 2, № 2. – С. 5–17. [Manukhina EB, Malyshev I.Yu. The role of nitric oxide in the development and prevention of endothelial dysfunction. Bulletin of Vitebsk State Medical University. 2003;2(2):5–17. (In Russ.)].Шабров А. В., Апресян А. Г., Добкес А. Л. и др. Современные методы оценки эндотелиальной дисфункции и возможности их применения в практической медицине // Рациональная фармакотерапия в кардиол. – 2016. – Т. 12, № 6. – С. 733–742. [Shabrov AV, Apresyan AG, Dobkes AL, Ermolov SU, Ermolova TV, Manasyan SG, Serdyukov SV. Current methods of endothelial dysfunction assessment and their possible use in the practical medicine. Rational Pharmacotherapy in Cardiology. 2016;12(6):733–742. (In Russ.)]. Doi: 10.20996/1819-6446-2016-12-6-733-742.Шабров А. В., Апресян А. Г., Добкес А. Л. и др. Современные методы оценки эндотелиальной дисфункции и возможности их применения в практической медицине // Рациональная фармакотерапия в кардиол. – 2016. – Т. 12, № 6. – С. 733–742. [Shabrov AV, Apresyan AG, Dobkes AL, Ermolov SU, Ermolova TV, Manasyan SG, Serdyukov SV. Current methods of endothelial dysfunction assessment and their possible use in the practical medicine. Rational Pharmacotherapy in Cardiology. 2016;12(6):733–742. (In Russ.)]. Doi: 10.20996/1819-6446-2016-12-6-733-742.Симаненкова А. В., Макарова М. Н., Васина Л. В. и др. Допплерография микроциркуляторного русла как способ оценки эндотелиопротективных свойств лекарственных препаратов у больных сахарным диабетом 2-го типа // Регионарное кровообращение и микроциркуляция. – 2018. – Т. 17, № 3. – С. 120–128. [Simanenkova AV, Makarova MN, Vasina LV, Butomo MI, Shlyakhto EV, Vlasov TD. Microcirculatory dopplerography as a method to evaluate drugs endothelial protective properties in type 2 diabetic patients. Regional blood circulation and microcirculation. 2018;17(3):120–128. (In Russ.)]. Doi: 10.24884/1682-6655-2018-17-3-120-128.Симаненкова А. В., Макарова М. Н., Васина Л. В. и др. Допплерография микроциркуляторного русла как способ оценки эндотелиопротективных свойств лекарственных препаратов у больных сахарным диабетом 2-го типа // Регионарное кровообращение и микроциркуляция. – 2018. – Т. 17, № 3. – С. 120–128. [Simanenkova AV, Makarova MN, Vasina LV, Butomo MI, Shlyakhto EV, Vlasov TD. Microcirculatory dopplerography as a method to evaluate drugs endothelial protective properties in type 2 diabetic patients. Regional blood circulation and microcirculation. 2018;17(3):120–128. (In Russ.)]. Doi: 10.24884/1682-6655-2018-17-3-120-128.Методы диагностики эндотелиальной дисфункции / А. Н. Иванов, А. А. Гречихин, И. А. Норкин, Д. М. Пучиньян // Регионарное кровообращение и микроциркуляция. – 2014. – Т. 13, № 4 (52). – С. 4–11. [Ivanov AN, Grechikhin AA, Norkin IA, Puchinyan DM. Methods of endothelial dysfunction diagnosis. Regional blood circulation and microcirculation. 2014;13(4(52)):4–11. (In Russ.)].Методы диагностики эндотелиальной дисфункции / А. Н. Иванов, А. А. Гречихин, И. А. Норкин, Д. М. Пучиньян // Регионарное кровообращение и микроциркуляция. – 2014. – Т. 13, № 4 (52). – С. 4–11. [Ivanov AN, Grechikhin AA, Norkin IA, Puchinyan DM. Methods of endothelial dysfunction diagnosis. Regional blood circulation and microcirculation. 2014;13(4(52)):4–11. (In Russ.)].

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