Role of immunological disorders, endothelial dysfunction and hemostatic disorders in the genesis of arterial hypertension in the metabolic syndrome
https://doi.org/10.15789/1563-0625-ROI-1926
Abstract
Mortality from diseases of the circulatory system is a challenge for the modern health care. Arterial hypertension (AH) mostly contributes to development of cardiovascular complications. It often proceeds against the background of metabolic disorders. Pathogenesis of hypertension is currently being considered a multifactorial disease. Pathogenesis of hypertension certainly has distinct features in presence of metabolic disorders,. Therefore, it is relevant to summarize current literature on the role of immunological disorders, endothelial dysfunction and hemostatic disorders in AH genesis during metabolic syndrome (MS). Most authors agree with existence of several mechanisms that determine relationships between AH and insulin resistance. Development of hypertension in MS patients with is a consequence of immunometabolic processes. Abdominal obesity is an important component of MS. It is associated with chronic inflammation of visceral adipose tissue, its excessive infiltration by immune cells, and increased production of adipokines and cytokines (TNFα, IL-6) with hypertension. AH is associated with a significant increase in T cells, that mediate endothelial dysfunction (ED) and provide a link between hypertension and subsequent atherosclerosis. T lymphocytes trigger a cascade of reactions. IL-17 is the end product of these events It is involved not only in increasing blood pressure, but also contributes to the development of vascular wall stiffness in АН patients. Thus, the relationship between several types of immune cells leads to inflammatory reactions, including those of vascular wall, initiating endothelial dysfunction. Chronic non-specific inflammation in MS, supported by the cytokine system, is a triggering mechanism for ED progression. Excessive production of endothelin-1 and inhibition of nitric oxide production are the classic markers of ED. Immune damage leads to imbalance in the production of vasoconstrictor and vasodilating substances, proliferative and antiproliferative factors in endothelium. It was shown that ED is an integral aspect of the insulin resistance syndrome in pathogenesis of arterial hypertension associated with metabolic disorders, and contributes to its worsening, increased vascular reactivity and further AH development. According to modern studies, it has been shown that excessive synthesis of pro-inflammatory cytokines introduces disturbances in the system of vascular hemostasis. When studying the effects of metabolic disorders upon hemostatic system, we may conclude that activation of fibrinolytic and plasma chains occurs in the same way for both men and women, with small gender characteristics of individual components. The rheological properties of the blood are also changed with developing MS. Systematization of the available literature data on the issue under study can serve as a basis for determining prognostic criteria of hypertension progression and risk of thrombotic complications.
About the Authors
E. I. PolozovaRussian Federation
Polozova Ella Ivanovna - PhD, MD (Medicine), Associate Professor, Professor, Department of Hospital Therapy.
430000, Republic of Mordovia, Saransk, Dimitrov str., 35/67, Phone: 7(927) 174-05-31
Competing Interests: not
E. V. Puzanova
Russian Federation
Puzanova Ekaterina Vladimirovna - Postgraduate Student, Department of Hospital Therapy.
Saransk, Republic of MordoviaCompeting Interests: not
A. A. Seskina
Russian Federation
Seskina Anastasia Alexandrovna - Postgraduate Student, Department of Hospital Therapy.
Saransk, Re public of Mordovia
Competing Interests: not
References
1. Afonasyeva T.M. Endothelial dysfunction. Opportunities for early diagnosis. Zhurnal nauchnykh statey “Zdorovye i obrazovanie v veke” = Journal of Scientific Articles “Health and Education Millennium”, 2016, Vol. 18, no. 11. pp. 101-104. (In Russ.)
2. Bespalova I.D., Ryazantseva N.V., Kalyuzhin V.V., Murashev B.Yu., Osikhov I.A., Medyantsev Yu.A., Afanasyeva D.S. Subpopulations and metabolic activity of blood mononuclear cells in metabolic syndrome. Meditsinskaya immunologiya = Medical Immunology (Russia), 2014, Vol. 16, no. 4, pp. 345-352. (In Russ.) doi: 10.15789/1563-0625-2014-4-345-352.
3. Bigaeva D.U., Daurova M.D., Gatagonova T.M., Bolieva L.Z. Features of structural and functional changes in the cardiovascular system in patients with arterial hypertension and chronic obstructive pulmonary disease [Electronic resource]. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education: Electronic Scientific Journal, 2014, no. 4. (In Russ.) Access mode: https://www.science-education.ru/ru/article/view?id=14483.
4. Boyarinova M.A., Rotar O.P., Konradi A.O. Adipokines and cardiometabolic syndrome. Arterialnaya gipertenziya = Arterial Hypertension, 2014, Vol. 20, no. 5, pp. 422-432. (In Russ.)
5. Bulaeva N.I., Golukhova E.Z. Endothelial dysfunction and oxidative stress: a role in the development of cardiovascular pathology. Kreativnaya kardiologiya = Creative Cardiology, 2013, no. 1, pp. 14-22. (In Russ.)
6. Vershinina A.M., Reut Yu.S., Gapon L.I., Busarova E.S., Tretyakova N.V, Kopylova L.N., Plyusnin A.V. Comparative efficacy of combined antihypertensive therapy in patients with arterial hypertension in combination with metabolic disorders. Meditsinskaya nauka i obrazovanie Urala = Medical Science and Education of the Ural, 2013, Vol. 14, no. 3 (75), pp. 14-17. (In Russ.)
7. Gerasimova A.S., Oleinikov V.E., Eliseeva I.V. Peculiarities of the course of arterial hypertension and target organ damage in the metabolic syndrome. Kardiologiya = Cardiology, 2008, no. 3, pp. 22-29. (In Russ.)
8. Ionov M.V., Zvartau N.E., Konradi A.O. Joint clinical recommendations of ESH / ESC 2018 for the diagnosis and management of patients with arterial hypertension: a first look. Arterialnaya gipertenziya = Arterial Hypertension, 2018, no. 24 (3), pp. 351-358. (In Russ.)
9. Islamgaleeva Z.M., Mingazetdinova L.N., Kabilova A.V, Bakirov A.B. The relationship of endothelial dysfunction with polymorphism of the SELP and VEGF genes in women with metabolic syndrome and arterial hypertension. Meditsinskiy vestnik Bashkortostana = Medical Journal of Bashkortostan, 2017, Vol. 12, no. 6 (72), pp. 21-26. (In Russ.)
10. nyazeva L.A., Shishova A.S., Goryainov I.I. The effect of therapy on markers of subclinical inflammation and stiffness of the vascular bed in patients with arterial hypertension with metabolic syndrome. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education, 2012, no. 6, p. 267. (In Russ.)
11. Kryukov N.N., Ginzburg M.M., Kiseleva E.V A modern view of the role of aseptic inflammation of adipose tissue in the genesis of obesity and metabolic syndrome. Arterialnaya gipertenziya = Arterial Hypertension, 2013, Vol. 19, no. 4, pp. 305-310. (In Russ.)
12. Litvinova L.S., Kirienkova E.V, Aksenova N.N., Gazatova N.D., Zatolokin P.A. Features of cellular immunity and cytokine repertoire in patients with metabolic syndrome. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2012, no. 3, pp. 53-57. (In Russ.)
13. Lyndina M.L., Shishkin A.N., Teslya O.V. Features of early diagnosis of endothelial dysfunction in patients with metabolic syndrome. Vestnik SPbGU = Bulletin of St. Petersburg State University, Ser. 11, 2014, Iss. 3, pp. 56-64. (In Russ.)
14. Mamedov M.N., Gorbunov V.M., Kiseleva N.V., Oganov R.G. Features of structural and functional changes in the myocardium and hemodynamic disorders in patients with metabolic syndrome: the contribution of arterial hypertension to the formation of total coronary risk. Kardiologicheskiy vestnik = Cardiological Bulletin, 2005, no. 1, pp. 11-16. (In Russ.)
15. Markov Kh.M. Molecular mechanisms of vascular endothelial dysfunction. Kardiologiya = Cardiology, 2005, no. 12, pp. 62-67. (In Russ.)
16. Nevzorova V.A., Pomogalova O.G., Nastradin O.V. The role of endothelial dysfunction in the progression of the metabolic syndrome from risk factors to vascular accidents. Tikhookeanskiy meditsinskiy zhurnal = Pacific Medical Journal, 2008, no. 3, pp. 69-74. (In Russ.)
17. Polozova E.I., Mamkina N.N., Seskina A.A., Puzanova E.V., Abramova S.G., Azizova E.Z. Diastolic dysfunction of the left ventricle in patients with metabolic syndrome and arterial hypertension. XLVI Ogaryovskiy Reading: Materials of Scientific Conference: in 3 hours. Part 2: Natural Sciences / ed. for issue P.V. Senin. Saransk]. Mordovia State University, 2018, pp. 352-357. (In Russ.)
18. Polozova E.I., Sorokina N.N., Seskina A.A., Puzanova E.V., Azizova E.Z., Abramova S.G. New opportunities for the diagnosis of cardiorenal disorders in metabolic syndrome. Innovations in education and medicine: Materials of the V All-Russian Scientific-practical Conference with International Participation. Makhachkala, 2018, pp. 235-240.
19. Polozova E.I., Sorokina N.N., Chegodaeva L.V., Trokhina I.E., Seskina A.A., Puzanova E.V. The study of renal dysfunction in patients with arterial hypertension and metabolic syndrome. Materials of the VI Eurasian Congress of Cardiology. Moscow, April 18-19, 2018, pp. 10-11.
20. Prokudina E.S., Maslov L.N., Ivanov V.V., Bespalova I.D., Pismenniy D.S., Voronkov N.S. The role of reactive oxygen species in the pathogenesis of adipocyte dysfunction in the metabolic syndrome: prospects for pharmacological correction. Vestnik RAMN = Annals of the Russian Academy of Medical Sciences, 2017, no. 72 (1), pp. 11-16. (In Russ.)
21. Salikhova A.F. Immunological aspects of the pathogenesis of arterial hypertension in the metabolic syndrome. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal, 2014, Vol. 95, no. 3, pp. 322-325. (In Russ.)
22. Sergeeva V.V., Rodionova A.Yu. A modern approach to the assessment of arterial hypertension in combination with metabolic disorders. Arterialnaya gipertenziya = Arterial Hypertension, 2013, Vol. 19, no. 5, pp. 397-404. (In Russ.)
23. Sidelnikova N.S., Yakusevich V.V., Petrochenko A.S., Tikhomirova I.A., Petrochenko E.P. Features of rheological and microcirculatory parameters in patients with metabolic syndrome. Yaroslavskiy pedagogicheskiy vestnik = Yaroslavl Pedagogical Bulletin, 2012, no. 2, pp. 91-97. (In Russ.)
24. Sumerkina V.A., Chulkov V.S., Chulkov V.S., Ozhigina E.V. The state of the hemostatic system and the cytokine profile in patients with metabolic syndrome. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal, 2015, Vol. 96, no. 5, pp. 728-734. (In Russ.)
25. Sumerkina V.A., Golovneva E.S., Telesheva L.F. Markers of endothelial dysfunction and the cytokine profile in patients with metabolic syndrome and abdominal obesity. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics, 2016, Vol. 61, no. 7, pp. 408-412. (In Russ.)
26. Sumerkina V.A., Chulkov Vl.S. Gender features of the blood coagulation system, carbohydrate and lipid metabolism in metabolic syndrome and isolated abdominal obesity. Izvestiya Samarskogo nauchnogo tsentra Rossiyskoy akademii nauk = Bulletin of the Samara Scientific Center of the Russian Academy of Sciences, 2014, Vol. 16, no. 5 (4), pp. 1422-1426. (In Russ.)
27. Тимашева Я.Р. Иммунологические аспекты эссенциальной гипертензии // Медицинская иммунология, 2019. Т. 21, № 3. С. 407-418. [Timasheva Ya.R. Immunological aspects of essential hypertension. Meditsinskaya immunologiya = Medical Immunology (Russia), 2019, Vol. 21, no. 3, pp. 407-418. (In Russ.)] doi: 10.15789/1563-0625-2019-3-407-418.
28. Feoktistova V.S., Vavilova T.V., Sirotkina O.V., Baldueva S.A., Gaykovaya L.B., Leonova I.A., Laskovets A.B., Ermakov A.I. A new approach to assessing endothelial dysfunction: determining the number of circulating endothelial cells by flow cytometry. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics, 2015, no. 4, pp. 23-39. (In Russ.)
29. Chazova I.E., Zhernakova Yu.V., Oshchepkova E.V. The prevalence of risk factors for cardiovascular diseases in the Russian population of patients with arterial hypertension. Kardiologiya = Cardiology, 2014, no. 10, pp. 4-12. (In Russ.)
30. Chazova I.E., Nedogoda S.V., Zhernakova Yu.V., Susekov A.V., Medvedeva I.V., Shestakova M.V. Recommendations for the management of patients with arterial hypertension with metabolic disorders. Kardiologicheskiy vestnik = Cardiological Bulletin, 2014, Vol. 9, no. 1, pp. 3-57. (In Russ.)
31. Chukaeva I.I., Orlova N.V., Khavka N.N., Klepikova M.V. The study of inflammatory factors in patients with metabolic syndrome. Lechebnoe delo = Medicine, 2010, no. 4, pp. 50-56. (In Russ.)
32. Chulkov V.S., Sumerkina V.A., Chulkov Vl.S. Estimation of the relationship of adipokine, cytokine, endothelial dysfunction markers and hemostasis indices with the state of target organs with a combination of arterial hypertension and abdominal obesity in young people. In the World of Scientific Discoveries, 2016, no. 6 (78), pp. 64-79. (In Russ.)
33. Caillon A., Mian M.O.R., Fraulob-Aquino J.C., Huo K.-G., Barhoumi T., Ouerd S., Sinnaeve P.R., Paradis P, Schiffrin E.L. уб T cells mediate angiotensin II-induced hypertension and vascular injuryclinical perspective. Circulation, 2017, Vol. 135, no. 22, pp. 2155-2162.
34. Caillon A., Schiffrin E.L. Role of inflammation and immunity in hypertension: Recent epidemiological, laboratory, and clinical evidence. Curr. Hypertens. Rep., 2016, Vol. 18, no. 3, 21. doi: 10.1007/s11906-016-0628-7.
35. Dinh Q.N., Drummond G.R., Kemp-Harper B.K., Diep H., de Silva T.M., Kim H.A., Sobey C.G. Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress. Aging, 2017, Vol. 9, no. 6, pp. 1595-1605.
36. Dzantieva E.O., Khripun I.A., Vorobev S.V., Gusova Z.R, Puzyreva V.P., Ibishev Kh.S., Belousov I.I. Chernyy A.A. Influence of sex hormones on the formation of endothelial dysfunction and cytokine imbalance in men with type 2 diabetes. Modern Problems of Science and Education, 2015, no. 6. Available at: https://science-education.ru/en/article/view?id=23526.
37. Espeli M., Smith K.G., Clatworthy M.R. FcyRIIB and autoimmunity. Immunol. Rev., 2016, Vol. 269, no. 1, pp. 194-211.
38. Fauchais A.L., Lallou F., Lise M.C., Boumediene A., Preud’homme J.L., Vidal E., Jauberteau M.O. Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival. J. Immunol., 2008, Vol. 181, no. 5, pp. 3027-3038.
39. Horigome H., Katayama Y., Yoshinaga M., Kato Y., Takahashi H., Sumazaki R. Significant associations among hemostatic parameters, adipokines, and components of the metabolic syndrome in Japanese preschool children. Clin. Appl. Thromb. Hemost., 2012, Vol. 18, no. 2, pp. 189-194.
40. Kobori H., Nangaku M., Navar L.G., Nishiyama A. The intrarenal renin-angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacol. Rev., 2007, Vol. 59, no. 3, pp. 251-287.
41. Krishnan S.M., Ling Y.H., Huuskes B.M., Ferens D.M., Saini N., Chan C.T., Diep H., Kett M.M., Samuel C.S., Kemp-Harper B.K., Robertson A.A.B., Cooper M.A., Peter K., Latz E., Mansell A.S., Sobey C.G., Drummond G.R., Vinh A. Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension. Cardiovasc. Res., 2019, Vol. 115, no. 4, pp. 776-787.
42. Liu X., Zhang Q., Wu H., Du H., Liu L., Shi H., Wang C., Xia Y., Guo X., Li C., Bao X., Su Q., Sun S., Wang X., Zhou M., Jia Q., Zhao H., Song K., Niu K. Blood neutrophil to lymphocyte ratio as a predictor of hypertension. Am. J. Hypertens., 2015, Vol. 28, no. 11, pp. 1339-1346.
43. Madhur M.S., Lob H.E., McCann L.A., Iwakura Y., Blinder Y., Guzik T.J., Harrison D.G. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension, 2010, Vol. 55, no. 2, pp. 500-507.
44. Marko L., Kvakan H., Park J.K., Qadri F., Spallek B., Binger K.J., Bowman E.P., Kleinewietfeld M., Fokuhl V, Dechend R., Muller D.N. Interferon-gamma signaling inhibition ameliorates angiotensin II-induced cardiac damage. Hypertension, 2012, Vol. 60, no. 6, pp. 1430-1436.
45. Mian M.O., Barhoumi T., Briet M., Paradis P., Schiffrin E.L. Deficiency of t-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses. J. Hypertens., 2016, Vol. 34, no. 1, pp. 97-108.
46. Moore J.P., Vinh A., Tuck K.L., Sakkal S., Krishnan S., Chan C., Lieu M., Samuel C.S., Diep H., Harper B.K., Tare M., Ricardo S.D., Guzik T.J., Sobey C.G., Drummond G.R. M2 macrophage accumulation in the aortic wall during angiotensin II infusion in mice is associated with fibrosis, elastin loss, and elevated blood pressure. Am. J. Physiol. Heart Circ. Physiol., 2015, Vol. 309, no. 5, pp. 906-917.
47. Norlander A.E., Madhur M.S., Harrison D.G. The immunology of hypertension. J. Exp. Med., 2018, Vol. 215, no. 1, p. 21-33.
48. Norlander A.E., Saleh M.A., Pandey A.K., Itani H.A., Wu J., Xiao L., Kang J., Dale B.L., Goleva S.B., Laroumanie F., Du L., Harrison D.G., Madhur M.S. A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage. JCI Insight, 2017, Vol. 2, no. 13, e92801. doi: 10.1172/jci.insight.92801.
49. O’Shea J.J., Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science, 2010, Vol. 327, no. 5969, pp. 1098-1102.
50. Ozyol A., Yucel O., Ege M.R., Zorlu A., Yilmaz M.B. Microalbuminuria is associated with the severity of coronary artery disease independently of other cardiovascular risk factors. Angiology, 2012, Vol. 63, no. 6, pp. 457-460.
51. Rubtsova K., Rubtsov A.V, Cancro M.P., Marrack P. Age-associated B cells: a T-bet-dependent effector with roles in protective and pathogenic immunity. J. Immunol., 2015, Vol. 195, no. 5, pp. 1933-1937.
52. Saleh M.A., McMaster W.G., Wu J., Norlander A.E., Funt S.A., Thabet S.R., Kirabo A., Xiao L., Chen W., Itani H.A., Michell D., Huan T., Zhang Y., Takaki S., Titze J., Levy D., Harrison D.G., Madhur M.S. Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation. J. Clin. Invest., 2015, Vol. 125, no. 3, pp. 1189-1202.
53. Selvaraj U.M., Poinsatte K., Torres V Heterogeneity of B cell functions in stroke-related risk, prevention, injury, and repair. Neurotherapeutics, 2016, Vol. 13, Iss. 4, pp. 729-747.
54. Singh M.V., Chapleau M.W, Harwani S.C., Abboud F.M. The immune system and hypertension. Immunol. Res., 2014, Vol. 59, no. 1-3, pp. 243-253.
55. Slarma S., Ghalaut V.S., Dixit R., Kumar S., George PJ. Microalbuminuria and C-reactive protein as a predictor of coronary artery disease in patient of acute chest pain. J. Cardiovasc. Dis. Res., 2013, Vol. 4, no. 1, pp. 37-39.
56. Vargas K.G., Kassem M., Mueller C., Wojta J., Huber K. Copeptin for the early rule-out of non-ST-elevation myocardial infarction. Int. J. Cardiol., 2016, no. 23, Vol. 223, pp. 797-804.
57. Winer D.A., Winer S., Chng M.H., Shen L., Engleman E.G. B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell. Mol. Life Sci., 2014, Vol. 71, no. 6, pp. 1033-1043.
Supplementary files
![]() |
1. Metadannye | |
Subject | arterial hypertension, metabolic disorders, metabolic syndrome, insulin resistance, nonspecific inflammation, immune disorders, endothelial dysfunction, hemostatic disorders | |
Type | Исследовательские инструменты | |
Download
(14KB)
|
Indexing metadata ▾ |
![]() |
2. Podpisi avtorov | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(744KB)
|
Indexing metadata ▾ |
![]() |
3. Titulnyi list | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(14KB)
|
Indexing metadata ▾ |
![]() |
4. Resume | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(15KB)
|
Indexing metadata ▾ |
![]() |
5. Statya na russkom yasike | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(38KB)
|
Indexing metadata ▾ |
![]() |
6. Statya na angl. yasike | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(30KB)
|
Indexing metadata ▾ |
![]() |
7. Spisok literaturi | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(43KB)
|
Indexing metadata ▾ |
![]() |
8. Spisok literaturi (tablica) | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(46KB)
|
Indexing metadata ▾ |
Review
For citations:
Polozova E.I., Puzanova E.V., Seskina A.A. Role of immunological disorders, endothelial dysfunction and hemostatic disorders in the genesis of arterial hypertension in the metabolic syndrome. Medical Immunology (Russia). 2020;22(2):221-230. (In Russ.) https://doi.org/10.15789/1563-0625-ROI-1926