Rational Pharmacotherapy in Cardiology

Advanced search

Abnormal Microcirculation and Red Blood Cell Function as a Cardiovascular Risk Factor in Metabolic Syndrome

Full Text:


The metabolic syndrome is a highly prevalent condition associated with increased cardiovascular risk in the population. Microvasculature is the terminal part of the cardiovascular system which primarily reacts to the increased secretion of the pro inflammatory adipokines typical for the metabolic syndrome. Microcirculation and blood cell abnormalities are the leading mechanisms of cardiovascular events development in this condition. Prevalence of microcirculation abnormalities and red blood cell dysfunction in metabolic syndrome and their role in the increased blood viscosity and cardiovascular events development are covered by the paper. The microcirculation abnormalities with a special focus on red blood cell dysfunction (impaired aggregation, stiffness) seen in metabolic syndrome and associated conditions are discussed in detail. The impact of abnormal red blood cell deformability (secondary to cholesterol accumulation in the cellular membranes) on the hemorheological abnormalities is revealed. Abnormal red blood cell surface charge due to proinflammatory changes associated with insulin resistance in diabetes mellitus is highlighted. These abnormalities lead to increased red blood cell aggregation and plasma viscosity that are the essential components of cardiovascular events pathogenesis. Their timely diagnosis is crucial for effective cardiovascular prevention.

About the Authors

V. I. Podzolkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Valery I. Podzolkov – MD, PhD, Professor, Head of Chair of Faculty Therapy №2

Trubetskaya ul. 8-2, Moscow, 119991

T. V. Koroleva
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Tatyana V. Koroleva – MD, PhD, Professor, Chair of Faculty Therapy №2

Trubetskaya ul. 8-2, Moscow, 119991

M. V. Pisarev
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Mikhail V.Pisarev – MD, PhD, Associate Professor, Chair of Faculty Therapy №2

Trubetskaya ul. 8-2, Moscow, 119991

M. G. Kudryavtseva
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Maria G. Kudryavtseva – MD, Postgraduate Student, Chair of Faculty Therapy №2

Trubetskaya ul. 8-2, Moscow, 119991

D. A. Zateyshchikova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Daria A. Zateyshchikova – MD, PhD, assistant professor, Chair of Faculty Therapy N2

Trubetskaya ul. 8-2, Moscow, 119991


1. O' Neill S., O'Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015;16(1):1-12. doi: 10.1111/obr.12229.

2. Achmegdanov N.M., Butrusova S.A., Dedov I.I., et al. Russian experts’ consensus on metabolic syndrome problem in the russian federation: defenition, diagnosis criteria, primary prevention and treatment. Rational Pharmacotherapy in Cardiology. 2010;6(4):599-606. (In Russ.)

3. Reaven G.M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607.

4. Grundy S.M. Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol. 2012;59(7):635-43. doi: 10.1016/j.jacc.2011.08.080.

5. Mottillo S., Filion K.B., Genest J., et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56(14):1113-32. doi: 10.1016/j.jacc.2010. 05.034.

6. Altabas V. Drug treatment of metabolic syndrome. Curr Clin Pharmacol. 2013;8(3):224-31. doi : 10.2174/1574884711308030009.

7. Vorobyeva E.N., Fomicheva M.L., Vorobiev R.I. Interrelation of cardiovascular diseases and metabolic syndrome. Atherosclerosis. 2015;11(2):50-7. (In Russ.)

8. Gao W. Does the constellation of risk factors with and without abdominal adiposity associate with different cardiovascular mortality risk? Int J Obes (Lond) 2008;32(5):757-62. doi: 10.1038/sj.ijo. 0803797.

9. Eberly L.E., Prineas R., Cohen J.D., et al. Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial. Diabetes Care. 2006;29(1):123-30. doi: 10.2337/diacare.29.01.06.dc05-1320.

10. Reaven G.M. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am. 2011;95(5):875-92. doi: 10.1016/j.mcna.2011.06.002.

11. Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab. 2013;27(2):163-77. doi: 10.1016/j.beem.2013.02.005.

12. Alexopoulos N., Katritsis D., Raggi P. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. 2014;233(1):104-12. doi: 10.1016/j.atherosclerosis.2013.12.023.

13. Rani V., Deep G., Singh R.K., et al. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183-93. doi: 10.1016/j.lfs.2016.02.002.

14. Peled N., Kassirer M., Shitrit D., et al. The association of OSA with insulin resistance, inflammation and metabolic syndrome. Respir Med. 2007;101(8):1696-701. doi: 10.1016/j.rmed.2007. 02.025.

15. Gutterman D.D., Chabowski D.S., Kadlec A.O., et al. The Human Microcirculation: Regulation of Flow and Beyond. Circ Res. 2016;118(1):157-72. doi: 10.1161/CIRCRESAHA.115.305364.

16. Liu Y., Gutterman D.D. Vascular control in humans: focus on the coronary microcirculation. Basic Res Cardiol. 2009;104(3):211-27. doi: 10.1007/s00395-009-0775-y.

17. Belin de chantemele E.J., Stepp D.W. Influence of obesity and metabolic dysfunction on the endothelial control in the coronary circulation. J Mol Cell Cardiol. 2012;52(4):840-7. doi: 10.1016/j.yjmcc.2011.08.018.

18. Podzolkov V.I., Bulatov V.P. The state of microcirculation in hypertension. In: Podzolkov VI, ed. Arterial hypertension. Moscow: MIA; 2016. (In Russ.)

19. Fagrell B., Intaglietta M. Microcirculation: its significance in clinical and molecular medicine. J Intern Med. 1997;241(5):349-62.

20. Pries A.R., Secomb T.W., Gessner T., et al. Resistance to blood flow in microvessels in vivo. Circ Res. 1994;75(5):904-15.

21. Cho Y.I., Mooney M.P., Cho D.J. Hemorheological disorders in diabetes mellitus. J Diabetes Sci Technol. 2008;2(6):1130-8. doi: 10.1177/193229680800200622.

22. Baskurt O.K., Meiselman H.J. Blood rheology and hemodynamics. Semin Thromb Hemost. 2003;29(5):435-50. doi: 10.1055/s-2003-44551.

23. Popel A.S., Johnson P.C. Microcirculation and Hemorheology. Annu Rev Fluid Mech. 2005;37:4369. doi: 10.1146/annurev.fluid.37.042604.133933.

24. Baskurt O.K., Meiselman H.J. Erythrocyte aggregation: basic aspects and clinical importance. Clin Hemorheol Microcirc. 2013;53(1-2):23-37. doi: 10.3233/CH-2012-1573.

25. Pretorius E., Olumuyiwa-Akeredolu O.O., Mbotwe S., et al. Erythrocytes and their role as health indicator: Using structure in a patient-orientated precision medicine approach. Blood Rev. 2016;30(4):263-74. doi: 10.1016/j.blre.2016.01.001.

26. Banerjee R., Nageshwari K., Puniyani R.R. The diagnostic relevance of red cell rigidity. Clin. Hemorheol. Microcic. 1988; 19 (1): 21-24

27. Radosinska J., Vrbjar N. The role of red blood cell deformability and Na,K-ATPase function in selected risk factors of cardiovascular diseases in humans: focus on hypertension, diabetes mellitus and hypercholesterolemia. Physiol Res. 2016;65 Suppl 1:S43-54.

28. Gyawali P., Richards R.S., Hughes D.L., et al. Erythrocyte aggregation and metabolic syndrome. Clin Hemorheol Microcirc. 2014;57(1):73-83. doi: 10.3233/CH-131792.

29. Soma P., Pretorius E. Interplay between ultrastructural findings and atherothrombotic complications in type 2 diabetes mellitus. Cardiovasc Diabetol. 2015;14:96. doi: 10.1186/s12933-015-0261-9.

30. Lee B.K., Durairaj A., Mehra A., et al. Hemorheological abnormalities in stable angina and acute coronary syndromes. Clin Hemorheol Microcirc. 2008;39(1-4):43-51.

31. Brun J.F., Varlet-Marie E., Fedou C., Raynaud de mauverger E. Are metabolically healthy obese patients also hemorheologically healthy? Clin Hemorheol Microcirc. 2015;61(1):39-46. doi: 10.3233/CH-141868.

32. Vayá A., Martínez M., Dalmau J., et al. Hemorheological profile in patients with cardiovascular risk factors. Haemostasis. 1996;26 Suppl 4:166-70. doi: 10.1159/000217294.

33. Vayá A., Hernández-Mijares A., Bonet E., et al. Association between hemorheological alterations and metabolic syndrome. Clin Hemorheol Microcirc. 2011;49(1-4):493-503. doi: 10.3233/CH2011-1499.

34. Zinchuk V.V. Deformability of erythrocytes: physiological aspects. Uspekhi Fiziologicheskikh Nauk. 2001;32(3):66-78. (In Russ.) [Зинчук В.В. Деформируемость эритроцитов: физиологические аспекты. Успехи Физиологических Наук. 2001;32(3):66-78.

35. Stuart J. Erythrocyte rheology. J Clin Pathol. 1985;38(9):965-77. doi: 10.1136/jcp.38.9.965.

36. De Oliveira S., Saldanha C. An overview about erythrocyte membrane. Clin Hemorheol Microcirc. 2010;44(1):63-74. doi: 10.3233/CH-2010-1253.

37. Barceló F., Perona J.S., Prades J., et al. Mediterranean-style diet effect on the structural properties of the erythrocyte cell membrane of hypertensive patients: the Prevencion con Dieta Mediterranea Study. Hypertension. 2009;54(5):1143-50. doi: 10.1161/HYPERTENSIONAHA.109.137471.

38. Kohno M., Murakawa K., Yasunari K., et al. Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients. Metab Clin Exp. 1997;46(3):287-91. doi: 10.1016/S0026-0495(97)90255-9.

39. Weijers R.N. Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus. Curr Diabetes Rev. 2012;8(5):390-400. doi : 10.2174/157339912802083531.

40. Banerjee R., Nageshwari K., Puniyani R.R. The diagnostic relevance of red cell rigidity. Clin Hemorheol Microcirc. 1998;19(1):21-4.

41. Shin S., Ku Y.H., Ho J.X., et al. Progressive impairment of erythrocyte deformability as indicator of microangiopathy in type 2 diabetes mellitus. Clin Hemorheol Microcirc. 2007;36(3):253-61.

42. Badalyan K.R., Vasilenko I.A., Fedin A.I. Biophysical properties of peripheral blood erythrocytes in patients with chronic cerebral ischemia. Lechebnoye Delo. 2015;1:84-90 (In Russ.).

43. Cowan A.Q., Cho D.J., Rosenson R.S. Importance of blood rheology in the pathophysiology of atherothrombosis. Cardiovasc Drugs Ther. 2012;26(4):339-48. doi: 10.1007/s10557-012-6402-4.

44. Devereux R.B., Case D.B., Alderman M.H., et al. Possible role of increased blood viscosity in the hemodynamics of systemic hypertension. Am J Cardiol. 2000;85:1265-8. doi: 10.1016/S00029149(00)00744-X.

45. Baskurt O.K., Yalcin O., Meiselman H.J. Hemorheology and vascular control mechanisms. Clin Hemorheol Microcirc. 2004;30(3-4):169-78.

46. Katyukhin L.N. To an explanation of the mechanism of the influence of shear stress on the viscous blood parameters in small diameter vessels. Science Rise. 2014; 5 (4): 24-9. (In Russ.)

47. Yedgar S., Koshkaryev A., Barshtein G. The red blood cell in vascular occlusion. Pathophysiol Haemost Thromb. 2002;32(5-6):263-8. doi: 10.1159/000073578.

48. Maeda N., Seike M., Nakajima T., et al. Contribution of glycoproteins to fibrinogen-induced aggregation of erythrocytes. Biochim Biophys Acta. 1990;1022(1):72-8. doi: 10.1016/00052736(90)90401-9.

49. Sidelnikova N.S., Yakusevich V.V., Petrochenko A.S. Features of rheological and microcirculatory indices in patients with metabolic syndrome. Yaroslavskiy Pedagogicheskiy Vestnik. 2012;2:91-7 (In Russ.)

50. Gromov A.A. Features of electrical and viscoelastic parameters of erythrocytes in patients with arterial hypertension of varying degrees. Sistemnyye Gipertenzii. 2012;9(4):59-64. (In Russ.)

51. Kurilovich S.A. Electrical parameters and structure of erythrocyte membranes in diffuse liver diseases. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2009;19(2):30-6. (In Russ.)

52. Surikova T.P., Zakharova V.D., Koroleva Т.V., et al. The study of the dependence of the erythrocyte charge in patients with diabetes mellitus, depending on the severity of its course. Astrakhanskiy Meditsinskiy Zhurnal. 2012;2(7):206-7. (In Russ.)

53. Kruchinina M.V., Gromov A.A., Parulikova M.V., et al. The possibilities of diagnosing rheology disorders in patients with type 2 diabetes mellitus. Modern problems of science and education. 2017; 5. [Cited by May 10, 2018. Available from: (In Russ.).

54. Podzolkov V.I., Koroleva T.V., Bragina A.Е., et al. Change in the functional state of erythrocytes as a component of microcirculatory disorders in metabolic syndrome. Rational Pharmacotherapy in Cardiology. 2018;14(2):184-9. (In Russ.)

55. Muravleva L.E. Charge balance of erythrocytes of patients with chronic pyelonephritis and arterial hypertension. Fundamental'nyye Issledovaniya. 2011;10-1:126-30. (In Russ.)

For citation:

Podzolkov V.I., Koroleva T.V., Pisarev M.V., Kudryavtseva M.G., Zateyshchikova D.A. Abnormal Microcirculation and Red Blood Cell Function as a Cardiovascular Risk Factor in Metabolic Syndrome. Rational Pharmacotherapy in Cardiology. 2018;14(4):591-597. (In Russ.)

Views: 425

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)