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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(3): 87-99


R.Yu. Marunych1, O.V. Gornytska1, A.V. Gudzenko2, O.A. Salnyk3, A.O. Hrabovskyi1, G.K. Bereznytskyj1, Ye.M. Makogonenko1

  1. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. PHEE “Kyiv Medical University”, Ukraine
  3. Taras Shevchenko National University of Kyiv, Ukraine


The structure and functions of the endothelium under normal conditions and a number of pathologies are reviewed in this work with the focus on its role in maintaining the balance between pro- and anticoagulant function of blood in different vascular beds. The role of endothelium in the synthesis and secretion of NO and other vascular regulators is highlighted. The mechanisms of its dysfunction, the role and interconnection of pathological changes in diseases such as atherosclerosis and hypertension are described.

Keywords: endothelium; hemostasis; dysfunction; pro- and anticoagulant function.


  1. Shevchenko YL, Astashev PE, Matveev SA, Gudymovich VG. The endothelium is the structural basis of the circulatory system: the history of the problem. NI Pirogov Bull Nat Med and Surgical Center. 2011; 6(2): 9-15. [Russian].
  2. Puzik SG. Endothelial disfunction in the pathogenesis of arterial hypertension and the progression of atherosclerosis. Family Med. 2018; 2(76): 69-74. [Russian]. CrossRef
  3. Krüger-Genge A, Block A, Franke RP, Jung F. Vascular Endothelial Cell Biology: An Update. Int J Mol Sci. 2019; 20(18): 4411-33. CrossRef PubMed PubMedCentral
  4. Lusher TF, Barton M. Biology of the endothelium. Clin Cardiology. 2007;20:3-10.
  5. Kitchens CS, Konkle BA, Kessler CM. Consultative hemostasis and thrombosis, 3rd ed. Philadelphia. Elsevier/ Saunders; 2013. p. 840. CrossRef
  6. Vita JA, Keaney JF. Endothelial function. Circulation. 2011;124(25):906-12. CrossRef PubMedCentral
  7. Dignat-George F, Boulanger CM. Themany faces of endothelial microparticles. Arterioscler Thromb Vasc Biol. 2011;31(1):27-33. CrossRef PubMed
  8. Malyars'ka NV, Kalinichenko MA. Endothelial dysfunction as a universal predictor of the development of cardiovascular pathology and the possibility of its correction in the practice of a family doctor. Medicines of Ukraine. 2017;1:38-41. [Ukrainian]. CrossRef
  9. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100(2):158-73. CrossRef PubMed
  10. Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012;2(1):1-22. CrossRef PubMed PubMedCentral
  11. Lupinskaya ZA, Zarif'yan AG, Gurovich TC, Shlejfer SG. Endothelium. Function and dysfunction. B.: KRSU; 2008. p. 373. [Russian].
  12. Minami T, Muramatsu M, Kume T. Organ/Tissue-Specific Vascular Endothelial Cell Heterogeneity in Health and Disease. Biol Pharm Bull. 2019;42(10):1609-19. CrossRef PubMed
  13. Petrishchev NN. Endothelial dysfunction. Pathogenetic significance and methods of correction. SPb.: IIC VMA; 2007. p. 296. [Russian].
  14. Alekseev NA. Hemorrhagic diathesis and thrombophilia. A guide for doctors. SPb: Gippokrat; 2004. p. 608. [Russian].
  15. Povzun SA. The most important syndromes: pathogenesis and pathological anatomy. SPb.: OOO «IPK «KOSTA»; 2009. p.408. [Russian].
  16. Rubanyi GM. The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol. 2013;22(Suppl. 4):S1-4. CrossRef PubMed
  17. Babichev A.V. The role of endothelium in hemostasis mechanisms. Pediatrician. SPb: 2013; 4(1): 122-7. [Russian]. CrossRef
  18. Vanhoutte P, Tang E. Endothelium-dependent contractions: when a good guy turns bad! J Physiol. 2008;586:5295-304. CrossRef PubMed PubMedCentral
  19. Madonna R, De Caterina r. Cellular and molecular mechanisms of vascular injury in diabetes. Part I: Pathways of vascular disease in diabetes. Vasc Pharmacol. 2011;54:68-74. CrossRef PubMed
  20. Madonna R, De Caterina R. Cellular and molecular mechanisms of vascular injury in diabetes. Part II: Cellular mechanisms and therapeutic targets. Vasc Pharmacol. 2011;54:75-9. CrossRef PubMed
  21. Li L, Chen W, Rezvan A, Jo H, Harrison GD. Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow. Arterioscler Thromb Vasc Biol. 2011;31:1547-54. CrossRef PubMed PubMedCentral
  22. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol. 2017;956:511-40. CrossRef PubMed
  23. Oikonomou E, Siasos G, Tsigkou V, Bletsa E, Panoilia ME, Oikonomou IN, Simanidis I, Spinou M, Papastavrou A, Kokosias G, Zaromitidou M, Stampouloglou P, Spartalis M, Vavuranalis M, Stefanadis C, Papavassiliou AG, Tousoulis D. Coronary artery disease and endothelial dysfunction: Novel diagnostic and therapeutic approaches. Curr Med Chem. 2019;144(3):253-67.
  24. Zuchi C, Tritto I, Carluccio E, Mattei C, Cattadori G, Ambrosio G. Role of endothelial dysfunction in heart failure. Heart Fail Rev. 2020;25(1):21-30. CrossRef PubMed
  25. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263-71. CrossRef PubMed
  26. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol. 2017;956:511-40. CrossRef PubMed
  27. Abrahamson EE, Ikonomovic MD. Brain injury-induced dysfunction of the blood brain barrier as a risk for dementia. Exp Neurol. 2020;238:113257. CrossRef PubMed
  28. Colbert JF, Schmidt EP. Endothelial and Microcirculatory Function and Dysfunction in Sepsis. Clin Chest Med. 2016;37(2):263-75. CrossRef PubMed PubMedCentral
  29. Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, Nishigaki I. The Vascular Endothelium and Human Diseases. Int J Biol Sci. 2013; 9(10):1057-69. CrossRef PubMed PubMedCentral
  30. Muxel S, Fasola F, Radmacher M. Endothelial functions: Translating theory into clinical application. Clin Hemorheol Microcirc. 2010;45:109-15. CrossRef PubMed
  31. Vozna HI, Moskalyuk VD, Sorohan VD. Endothelium: functional properties and its dysfunction (review of the literature with materials of own researches). Clin Exp Pathol. 2015;14,1(51):209-14. [Ukrainian].
  32. Sagach V, Bondarenko A, Bazilyuk O, Kotsuruba A. Endothelial dysfunction: Possible mechanisms and ways of correction. Exp Clin Cardiol. 2006;11(2):107-10.
  33. Andrawis N, Jones DS, Abernethy DR. Aging is associated with endothelial dysfunction in the human forearm vasculature. J Am Geriartr Soc. 2000;48:193-8. CrossRef
  34. Ungvari Z, Tarantini S, Kiss T, Wren JD, Giles CB, Griffin CT, Murfee WL, Pacher P, Csiszar A. Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. Nat Rev Cardiol. 2018;15(9):555-65. CrossRef PubMed PubMedCentral
  35. Ostroumova OD, Dubinskaya RE. Aging and endothelial dysfunction. Cardiovascular Ther Prev. 2004;3(4):83-9. [Russian].
  36. Hoffmann J, Haendler J, Aicher A, Rössig L, Vasa M, Zeiher AM, Dimmeler S. Aging enchances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide. Circ Res. 2001;29:709-15. CrossRef PubMed
  37. Avdeeva IV, Burko NV, Sumenkova AO, Olejnikov VE. Early vascular aging: what do we know about it today? Internat Med J. 2018;3:5-10. [Russian].
  38. Bocharov SN, Kulinskij VI. Protective strategies of the body in anesthesiology and resuscitation. Irkutsk. 2003;134. [Russian].
  39. Dolgih VT, Razgonov FI, Shikunova LG. Disorders of blood coagulation properties in the early post-resuscitation period and their prevention. Anesthesiol Resusc. 2004; 6:35-40. [Russian].
  40. Faber DR, de Groot PG, Visseren FL. Role of adipose tissue in haemostasis, coagulation and fibrinolysis. Obesity Rev. 2009;10:554-63. CrossRef PubMed
  41. Suprun EV, Tereshchenko SV. The role of endothelial dysfunction in the formation of complications of diabetes mellitus and the prospects for its correction with interleukin-1 receptor antagonist. Bull Sci Achiev. 2017; 2:5-12. [Russian].
  42. Barton M, Baretella O, Meyer MR. Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction. Br J Pharmacol. 2012;165(3):591-602. CrossRef PubMed PubMedCentral
  43. Paneni F, Costantino S, Cosentino F. Role of oxidative stress in endothelial insulin resistance. World J Diabetes. 2015;6(2):326-32. CrossRef PubMed PubMedCentral
  44. Hripun IA, Vorob'ev SV, Kogan MI. Interrelation of androgen receptor gene polymorphism and endothelial function in men with type 2 diabetes. Diabetes. 2015;18(4):35-40. [Russian]. CrossRef
  45. Carcamo-Orive I, Huang NF, Quertermous T, Knowles JW. Induced Pluripotent Stem Cell Derived Endothelial Cells in Insulin Resistance and Metabolic Syndrome. Arterioscler Thromb Vasc Biol. 2017;37(11):2038-42. CrossRef PubMed PubMedCentral
  46. Cosentino F, Luscher TF. Endothelial dysfunction in diabetes mellitus. J Cardiovasc Pharmacol. 1998;32(Suppl 3):S54-61.
  47. Vlasov SV. The role of endothelium in the regulation of the aggregate state of blood. Polytrauma. 2010;(4):84-9. [Russian].
  48. Clerk LH, Vincent MA, Lindner JR, Clark MG, Rattigan S, Barrett EJ. The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptake. Diabetes Metab Res Rev. 2004;20:3-12. CrossRef PubMed
  49. Zharinova VY. Endothelial dysfunction as a multidisciplinary problem. Blood Circ Hemost. 2015;1,2:9-15. [Russian].
  50. Yarek-Martynova IR, Shestakova MV. Diabetes mellitus and endothelial dysfunction. Diabetes. 2004;2:48-52. [Russian]. CrossRef
  51. Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. 2013;10(6):472-82. CrossRef PubMed
  52. Nikolaev KY, Bajramova SS, Cygankova OV, Lifshic GI. Endothelium-dependent vascular reactivity in type 2 diabetes. Clin Pract. 2017;4:61-5. [Russian]. CrossRef
  53. Temelkova-Kurktschiev T, Koehler C, Henkel E. Glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbAlc level. Diabetes Care. 2000;23:1830-34. CrossRef PubMed
  54. de Mattia G, Bravi MC, Laurenti O, Cassone-Faldetta M, Proietti A, De Luca O, Armiento A, Ferri C. Reduction of oxidative stress by oral N-acetyl-Lcysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, nondyslipidaemic, normotensive, patients with non-insulindependent diabetes. Diabetol. 1998;41:1392-96. CrossRef PubMed
  55. Watts GF, Playford DA. Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in non-insulin dependent diabetes mellitus: a hypothesis. Atherosclerosis. 1998;141:17-30. CrossRef
  56. Atawia RT, Bunch KL, Toque HA, Caldwell RB, Caldwell RW. Front Biosci (Landmark Ed). Mechanisms of obesity-induced metabolic and vascular dysfunctions. 2019;24:890-934. CrossRef PubMed
  57. Meigs JB, O'donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, Nathan DM, Sullivan LM, D'Agostino RB, Wilson PWF. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. Diabetes. 2006;55(2):530-37. CrossRef PubMed
  58. Jude EB, Oyibo SO, Chalmers N. Peripheral arterial disease in diabetic and nondiabetic patients. Diabetes Care. 2001;24:1433-37. CrossRef PubMed
  59. Kasatkina SG, Kasatkin SN. The value of endothelial dysfunction in patients with type 2 diabetes. Basic Res. 2011;7:248-52. [Russian].
  60. Vlasov TD, Nesterovich II, Endothelial dysfunction: from particular to general. Return to the "old paradigm"? Regional Blood Circ Microcirc. 2019;18(2):19-27. [Russian]. CrossRef
  61. Dunaevskaya SS, Vinnik YS. The development of endothelial dysfunction in obliterating atherosclerosis of the vessels of the lower extremities and markers for predicting the course of the disease. Bull of Siberian Medicine. 2017;16(1):108-18. [Russian]. CrossRef
  62. Poloneckij OL, Poloneckij LZ. Endothelial dysfunction and atherosclerosis. Med News. 2012;6:6-11. [Russian].
  63. Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620-3. CrossRef PubMed PubMedCentral
  64. Sima AV, Stancu CS, Simionescu M. Vascular endothelium in atherosclerosis. Cell Tissue Res. 2009;335(1):191-203. CrossRef PubMed
  65. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-74. CrossRef PubMed
  66. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. New Engl J Med. 2005;352:1685-95. CrossRef PubMed
  67. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nature reviews. Immunol. 2006; 6:508-19. CrossRef PubMed
  68. Schwartz SM, Galis ZS, Rosenfeld ME, Falk E. Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol. 2007;27:705-13. CrossRef PubMed
  69. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46:937-54. CrossRef PubMed
  70. Libby P. Mechanisms of acute coronary syndromes. N Engl J Med. 2013;369:883-4. CrossRef
  71. Quillard T, Araujo HA, Franck G, Shvartz E, Sukhova G, Libby P. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur Heart J. 2015;36:1394-404. CrossRef PubMed PubMedCentral
  72. Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4): 620-36. CrossRef PubMed PubMedCentral
  73. Yarmysh NV, Groznaya LN. Endothelial dysfunction and its regulatory factors. Bull of problems of biol and med. 2014;2(111), Issue 3:37-43. [Russian].
  74. Davis ME, Grumbach IM, Fukai T, Cutchins A, Harrison DG. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem. 2004; 279:163-8. CrossRef PubMed
  75. Zimnickaya OV, Petrova MM. Features of endothelial dysfunction in hypertension. Med Alphabet. 2019;1(3):29-33. [Russian]. CrossRef
  76. Minshall RD, Paria BC, Vogel SM, Malik AB. Role of Ca2+ Signaling in the Regulation of Endothelial Permeability Chinnaswamy Tiruppathi 1. Vasc Pharmacol. 2002;39 (4-5):173-85. CrossRef
  77. Suehiro J, Hamakubo T, Kodama T, Aird WC, Minami T. Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3. Blood. 2010;115(12):2520-32. CrossRef PubMed PubMedCentral
  78. Nathaniel G dela Paz, Walshe TE, Leach LL, SaintGeniez M, D'Amore PA. Role of Shear-Stress-Induced VEGF expression in endothelial cell survival. J Cell Sci. 2012;125(Pt 4):831-43. CrossRef PubMed PubMedCentral
  79. Thuiller C, Richard V. Targeting endothelial dysfunction in hypertensive subjects. J Hum Hypertension. 2005;19:21-5. CrossRef PubMed
  80. Bojcov SA. Vessels as a springboard and target of arterial hypertension. Diseases of the heart and blood vessels. 2006;1(3):35-40. [Russian].
  81. Koryakina LB, Pivovarov YI, Kuril'skaya TE, Sergeeva AS, Kurilskaya, A.S. Sergeeva, I. V. Babushkina. Vascular endothelial dysfunction in arterial hypertension and coronary heart disease (literature review). Bull ESSC SB RAMS. 2013;2(90),(Pt 1):165-70. [Russian].
  82. Shishkin AN, Lyndina ML. Endothelial dysfunction and arterial hypertension. Arterial Hypertension. 2008;4(14):315-19. [Russian]. CrossRef
  83. Shishkin AN. Modern strategy of therapy for endothelial dysfunction from the standpoint of evidence-based medicine. Med Statements.. 2008; 3(45): 6-19. [Russian]. CrossRef
  84. Sagach VF, Bazilyuk OV, Kotsyuruba AV, Bukhanevich OM. Disorders of endothelium-dependent vascular reactions, arginase and NO-synthase pathways of L-argenin metabolism in hypertension. Fiziol. Zh. 2000; 3(46): 3-13. [Ukrainian].
  85. Namakanov BA, Rasulov MM. Endothelial dysfunction in arterial hypertension is a risk factor for cardiovascular disorders. Cardiovasc Therapy Prevent. 2005;4(6),(Pt 2):98-101. [Russian].
  86. Soloviev A, Lehen'kyi V, Zelensky S, Hellstrand P, Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of myofilaments, Cell Calcium. 2004; 2(36): 165-73. CrossRef PubMed
  87. Li Q, Yon JY, Cai H. Mechanisms and Consequences of eNOS Dysfunction in Hypertension. J Hypertens. 2015;33(6):1128-36. CrossRef PubMed PubMedCentral
  88. Lip, PL, Jones AF, Price N, Headon M, Beevers DG, Lip GY. Do intraocular angiotensin II levels, plasma prothrombotic factors and endothelial dysfunction contribute to proliferative diabetic retinopathy? Acta Ophthalmol Scand. 1998;76(5):533-36. CrossRef PubMed
  89. Freestone B, Chong AY, Nuttall S, Blann AD, Lip GY. Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body nitrate/nitrite product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation. Chest. 2007;132(4):1253-8. CrossRef PubMed
  90. Popova AA, Mayanskaya SD, Mayanskaya NN, Berezikova EN, Hidirova LD. Arterial hypertension and endothelial dysfunction (part I). Bull Modern Clin Med. 2009;2(Pt 2):41-6. [Russian]. CrossRef
  91. Seedorf G, Metoxen AJ, Rock R, Markham N, Ryan S, Vu T, Abman SH. Hepatocyte growth factor as a downstream mediator of vascular endothelial growth factor-dependent preservation of growth in the developing lung. Am J Physiol Lung Cell Mol Physiol. 2016;310(11):1098-110. CrossRef PubMed PubMedCentral
  92. Karoli NA, Rebrov AP. Endothelial dysfunction and its clinical significance in patients with chronic obstructive pulmonary disease. Clin Med. 2005;(9):10-5. [Russian].
  93. Volkov GL, Platonova TN, Savchuk AN, Gornickaya OV, Chernyshenko TM, Krasnobrizhaya EN. Modern ideas about the hemostasis system. K.: Naukova dumka; 2005. p. 296. [Ukrainian].
  94. Xin X, Yang S, Ingle G, Zlot C, Rangell L, Kowalski J. Et al. Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Am J Pathol. 2001; 158(3):1111-20. CrossRef
  95. Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf). 2017; 219(1):22-96. CrossRef PubMed

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