Ex vivo observation of the thromboinflammation process in patients with chronic heart failure

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Abstract

BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide. Chronic heart failure is accompanied by hemodynamic disturbances, including alterations in blood microrheological properties. Changes in erythrocyte deformability may lead to impaired activation and interaction of platelets and neutrophils, contributing to thrombosis and the progression of chronic heart failure.

AIM: Determination of neutrophil activity and thrombus formation in an ex vivo model of thromboinflammation in patients with chronic heart failure with simultaneous assessment of blood microrheology.

METHODS: The study involved 21 patients with a diagnosis of chronic heart failure and 8 healthy volunteers. The patients and volunteers underwent determination of the biochemical composition of blood plasma and assessment of the condition of the blood elements. The thromboinflammation was evaluated in whole heparinized blood using parallel-flat flow chambers coated with type I collagen at a shear rate of 100 1/s. The deformability parameters of erythrocytes were measured in vitro using the method of laser diffractometry. Erythrocyte aggregation was determined by diffuse light scattering from whole blood samples.

RESULTS: For thrombus areas, no statistical differences were found between healthy controls and patients with chronic heart failure. However, the neutrophil velocities for patients with chronic heart failure were significantly lower than for healthy controls (0.11 ± 0.02 µm/s for chronic heart failure versus 0.16 ± 0.04 µm/s for healthy controls). The thrombus areas for patients with chronic heart failure at 5 and 10 minutes of growth correlated with the concentration of red blood cells and the average volume of red blood cells. Also, the aggregation coefficients of erythrocytes A1 and A2 characterizing the intensity of the process of formation of linear and three-dimensional aggregates positively correlated with thrombus area. In addition, mean corpuscular volume, erythrocyte deformability indices, and yield strength of the erythrocytes correlated with neutrophil movement velocities.

CONCLUSION: Thus, although there is no significant change in thrombus formation in chronic heart failure, however, we can talk about a decrease in neutrophil activity, possibly associated with the increase in blood viscosity.

About the authors

Julia Jessica D. Korobkina

Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences

Email: juliajessika@gmail.com
ORCID iD: 0000-0002-2762-5460
SPIN-code: 6630-3657

Postgraduate Student

Russian Federation, Moscow

Sofia V. Galkina

Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Email: s_v_galkina@rambler.ru
ORCID iD: 0009-0006-6321-4489

Postgraduate Student; Laboratory Research Assistant

Russian Federation, Moscow; Moscow

Andrey Е. Lugovtsov

Lomonosov Moscow State University

Email: anlug1@gmail.com
ORCID iD: 0000-0001-5222-8267

Cand. Sci. (Physics and Mathematics), Senior Researcher at the Faculty of Physics

Russian Federation, Moscow

Nikita А. Mironov

Lomonosov Moscow State University

Email: nikimir29@mail.ru
ORCID iD: 0000-0001-6729-4371

Postgraduate Student at the Medical Scientific and Educational Institute

Russian Federation, Moscow

Larisa I. Dyachuk

Lomonosov Moscow State University

Email: cardio-heart@yandex.ru
ORCID iD: 0000-0003-0368-9408

MD, Cand. Sci. (Medicine), Head of the Cardiology Department of the Hospital, Cardiologist at the Medical Scientific and Educational Institute

Russian Federation, Moscow

Yana A. Orlova

Lomonosov Moscow State University

Email: YAOrlova@mc.msu.ru
ORCID iD: 0000-0002-8160-5612

MD, Dr. Sci. (Medicine), Head of the Department of Age-Associated Diseases, Cardiologist at the Medical Scientific and Educational Institute

Russian Federation, Moscow

Alexander V. Priezzhev

Lomonosov Moscow State University

Email: avp2@mail.ru
ORCID iD: 0000-0003-4216-7653

Cand. Sci. (Physics and Mathematics), Associate Professor at the Faculty of Physics

Russian Federation, Moscow

Anastasia N. Sveshnikova

Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; Lomonosov Moscow State University

Author for correspondence.
Email: ASve6nikova@yandex.ru
ORCID iD: 0000-0003-4720-7319
SPIN-code: 7893-4627

Dr. Sci. (Physics and Mathematics), Head of the Laboratory of Intracellular Signaling and Systems Biology; Head of the Laboratory of Cell Biology and Translational Medicine; Professor at the Faculty of Fundamental Physicochemical Engineering

Russian Federation, Moscow; Moscow; Moscow

References

  1. Miličić D, Jakuš N, Fabijanović D. Microcirculation and heart failure. Curr Pharm Des. 2018;24(25):2954–2959. doi: 10.2174/1381612824666180625143232
  2. Tikhomirova I, Petrochenko E, Muravyov A, et al. Microcirculation and blood rheology abnormalities in chronic heart failure. Clin Hemorheol Microcirc. 2017;65(4):383–391. doi: 10.3233/CH-16206
  3. Del Buono MG, Montone RA, Camilli M, et al. Coronary microvascular dysfunction across the spectrum of cardiovascular diseases. J Am Coll Cardiol. 2021;78(13):1352–1371. doi: 10.1016/j.jacc.2021.07.042
  4. Guizouarn H, Barshtein G. Editorial: red blood cell vascular adhesion and deformability, volume II. Front Physiol. 2022;13:849608. doi: 10.3389/fphys.2022.849608
  5. Mohaissen T, Proniewski B, Targosz-Korecka M, et al. Temporal relationship between systemic endothelial dysfunction and alterations in erythrocyte function in a murine model of chronic heart failure. Cardiovasc Res. 2022;18(12):2610–2624. doi: 10.1093/cvr/cvab306
  6. Chang H-Y, Yazdani A, Li X, et al. Quantifying platelet margination in diabetic blood flow. Biophys J. 2018;115(7):1371–1382. doi: 10.1016/j.bpj.2018.08.031
  7. Czaja B, Gutierrez M, Závodszky G, et al. The influence of red blood cell deformability on hematocrit profiles and platelet margination. PLOS Comput Biol. 2020;16:e1007716. doi: 10.1371/journal.pcbi.1007716
  8. Spann AP, Campbell JE, Fitzgibbon SR, et al. The effect of hematocrit on platelet adhesion: experiments and simulations. Biophys J. 2016;111(3):577–588. doi: 10.1016/j.bpj.2016.06.024
  9. Oh D, Ii S, Takagi S. Numerical study of particle margination in a square channel flow with red blood cells. Fluids. 2022;7:96. doi: 10.3390/fluids7030096
  10. Sloop GD, De Mast Q, Pop G, et al. The role of blood viscosity in infectious diseases. Cureus. 2020. Vol. 12, N 2. P. e7090. doi: 10.7759/cureus.7090
  11. Jafri SM, Ozawa T, Mammen E, et al. Platelet function, thrombin and fibrinolytic activity in patients with heart failure. Eur Heart J. 1992;14(2):205–212. doi: 10.1093/eurheartj/14.2.205
  12. Popovic B, Zannad F, Louis H, et al. Endothelial-driven increase in plasma thrombin generation characterising a new hypercoagulable phenotype in acute heart failure. Int J Cardiol. 2019;274:195–201. doi: 10.1016/j.ijcard.2018.07.130
  13. Antipenko S, Mayfield N, Jinno M, et al. Neutrophils are indispensable for adverse cardiac remodeling in heart failure. J Mol Cell Cardiol. 2024;189:1–11. doi: 10.1016/j.yjmcc.2024.02.005
  14. Sveshnikova AN, Adamanskaya EA, Panteleev MA. Conditions for the implementation of the phenomenon of programmed death of neutrophils with the appearance of DNA extracellular traps during thrombus formation. Pediatr Hematol Immunopathol. 2024;23:211–218. doi: 10.24287/1726-1708-2024-23-1-211-218
  15. Korobkin JD, Deordieva EA, Tesakov IP, et al. Dissecting thrombus-directed chemotaxis and random movement in neutrophil near-thrombus motion in flow chambers. BMC Biol. 2024;22(1):115. doi: 10.1186/s12915-024-01912-2
  16. Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906–918. doi: 10.1182/blood-2018-11-882993
  17. Sveshnikova AN, Adamanskaya EA, Korobkina YuD, Panteleev MA. Intracellular signaling involved in the programmed neutrophil cell death leading to the release of extracellular DNA traps in thrombus formation. Pediatr Hematol Immunopathol. 2024;23(2):222–230. doi: 10.24287/1726-1708-2024-23-2-222-230
  18. Tracchi I, Ghigliotti G, Mura M, et al. Increased neutrophil lifespan in patients with congestive heart failure. Eur J Heart Fail. 2009;11(4):378–385. doi: 10.1093/eurjhf/hfp031
  19. Tang X, Wang P, Zhang R, et al. KLF2 regulates neutrophil activation and thrombosis in cardiac hypertrophy and heart failure progression. J Clin Invest. 2022;132:e147191. doi: 10.1172/JCI147191
  20. Morozova DS, Martyanov AA, Obydennyi SI, et al. Ex vivo observation of granulocyte activity during thrombus formation. BMC Biol. 2022;20(1):32. doi: 10.1186/s12915-022-01238-x
  21. Nechipurenko DY, Receveur N, Yakimenko AO, et al. Clot contraction drives the translocation of procoagulant platelets to thrombus surface. Arterioscler Thromb Vasc Biol. 2019;39(1):37–47. doi: 10.1161/ATVBAHA.118.311390
  22. Ermolinskiy PB, Lugovtsov AE, Maksimov MK, et al. Interrelation of blood microrheological parameters measured by optical methods and whole blood viscosity in patients suffering from blood disorders: a pilot study. J Biomed Photonics Eng. 2024;10(2):020306. doi: 10.18287/JBPE24.10.020306
  23. Priezzhev AV, Lee K, Firsov NN, Lademann J. Optical study of RBC aggregation in whole blood samples and single cells. In: Handbook of Optical Biomedical Diagnostics. Second Edition. Volume 2: Methods. SPIE PRESS; 2016.
  24. Gromotowicz-Poplawska A, Marcinczyk N, Misztal T, et al. Rapid effects of aldosterone on platelets, coagulation, and fibrinolysis lead to experimental thrombosis augmentation. Vascul Pharmacol. 2019;122–123:106598. doi: 10.1016/j.vph.2019.106598
  25. Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. Semin Thromb Hemost. 2024;50(6):902–915. doi: 10.1055/s-0043-1777802

Supplementary files

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2. Fig. 1. Determination of thromboinflammatory status in patients with chronic heart failure (СНF). a, Parallel-plate flow chamber and a typical field of view from a healthy donor at the 25th minute of the experiment. Composite image (stained with DiOC(6), Hoechst 33342, and Annexin V-Alexa 647). Dashed line indicates the location of the growing thrombus, neutrophils are outlined, arrows indicate neutrophil migration trajectories. Scale bar: 25 μm. b, Thrombus areas in patients with СНF and healthy donors (HD) at 300, 600, and 1500 seconds of imaging. c, Thrombus formation in patients with different body mass index (BMI) at 300 seconds. d, Neutrophil migration speed in patients with chronic heart failure and healthy donors. * p < 0.05, ns, no statistically significant differences. Statistical significance calculated using the Mann–Whitney test.

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3. Fig. 2. Correlation of thrombus area at 300 seconds with parameters of RBC aggregation A1 (a) and A2 (b), with an increase in RBC concentration (c), with RBC concentration at 600 seconds (r = 0.4, p < 0.05) (d). Linear interpolation of data (solid line) and 95% confidence intervals (dashed line) are provided.

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4. Fig. 3. Correlation of neutrophil movement velocity with the erythrocyte deformability parameter E3 (a), with the yield strength of the erythrocytes (b), with the aggregation parameter A2 of the erythrocyte suspension (c), with the erythrocyte width (d) by volume distribution for generalized data on patients and healthy donors. Linear interpolation of the data (solid line) and 95% confidence intervals (dashed line) are shown.

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