Influence of sulodexide at endothelial and blood cell condition in COVID-19 patients


Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

In spite of the fact that the most expressed manifestation of COVID-19 is severe pulmonary damage, it is shown by clinical observations that other organs are often affected too in that infection. This multi-organ pathology is caused by disorders in haemostasis and endothelial function. Since there are no medicaments that can directly inhibit the activity of SARS-CoV-2, the effort to mitigate its damaging effects by protecting the endothelium and preventing hemostasis disruption looks to be essential. We investigated the ability of sulodexide, which is a mixture of a fast heparin fraction (80%) and dermatan sulfate (20%), to have a therapeutic effect in COVID 19. Material and methods. 28 patients with moderate COVID-19 were engaged in a single-center, prospective, observational study. Patients in the control group (n=14) were treated using the therapy according to the Ministry of Healthcare recommendations, and patients in the experimental group (n=14) received daily intravenous injections of sulodexide (600 units) in addition to this therapy for ten days. Blood samples were obtained from the ulnar vein on admission and 10 days later and were examined by scanning electron microscopy. Results. Sulodexide significantly reduced the concentration of circulating endothelial cells. That indicated its ability to protect the endothelium from the damaging effects of the virus. It also prevented additional platelet activation and erythrocyte aggregation, which inhibited the normal passage of these cells through the capillaries. Conclusion. The results showed that sulodexide is able to prevent thrombosis and suppress vascular inflammation. This makes it to be a promising treatment remedy for COVID-19 patients, although a randomised trial on a large number of patients is needed to validate this conclusion.

Texto integral

Acesso é fechado

Sobre autores

Lyudmila Buryachkovskaya

Academician E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Healthcare of Russia

Email: livbur@mail.ru
D.Sc.(Biology), leading researcher 121552 Moscow, 15a, 3rd Cherepkovskaya Str

Arthur Melkumyants

Academician E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Healthcare of Russia; Moscow Institute of Physics and Technology (National Research University)

Email: artmelk@gmail.com
D.Sc.(Biology), professor, leading researcher 121552 Moscow, 15a, 3rd Cherepkovskaya Str

Nikita Lomakin

Central Clinical Hospital with Polyclinic of the Administrative Department of the President of the Russian Federation; Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia

Email: lomakinnikita@gmail.com
Dr. med. habil., chief external expert cardiologist of Russian Presidential Administration, head of the Department of emergency cardiology and cardiac resuscitation; head of the Department of cardiology 125993, Moscow, 2/1 bld.1 Barrikadnaya Str

Olga Antonova

Academician E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Healthcare of Russia

researcher at Academician 121552 Moscow, 15a, 3rd Cherepkovskaya Str

Vladimir Ermishkin

Academician E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Healthcare of Russia

PhD in Medicine, leading researcher 121552 Moscow, 15a, 3rd Cherepkovskaya Str

Yulia Dotsenko

Academician E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Healthcare of Russia

PhD., researcher 121552 Moscow, 15a, 3rd Cherepkovskaya Str

Bibliografia

  1. Zhu N., Zhang D., Wang W. et al. A novel coronavirus from patients with pneumonia in China, 2019. New Engl J Med. 2020; 382(8): 727-33. https://dx.doi.org/10.1056/NEJMoa2001017.
  2. Wiersinga W.J., Rhodes A., Cheng A.C. et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review. JAMA. 2020; 324(8): 782-93. https://dx.doi.org/10.1001/jama.2020.12839.
  3. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020; 323(13): 1239-42. https://dx.doi.org/10.1001/jama.2020.2648.
  4. Chen N., Zhou M., Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020; 395(10223): 507-13. https://dx.doi.org/10.1016/S0140-6736(20)30211-7.
  5. Prabakaran P., Xiao X., Dimitrov D. A model of the ACE-2 structure and function as a SARS-CoV receptor. Biochem Biophys Res Commun. 2004; 314(1): 235-41. https://dx.doi.org/10.1016/j.bbrc.2003.12.081.
  6. Zaim S., Chong J., Sankaranarayanan V., Harky A. COVID-19 and multi-organ response. Curr Probl Cardiol. 2020; 45(8): 100618. https://dx.doi.org/10.1016/j.cpcardiol.2020.100618.
  7. Маев И.В., Шпектор А.В., Васильева Е.Ю. Новая коронавирусная инфекция COVID-19: экстрапульмональные проявления. Терапевтический архив. 2020; 92(8): 4-11. https://dx.doi.org/10.26442/00403660.2020.08.000767. EDN: TDYYCY.
  8. Kochi A., Tagliari A., Forleo G. et al. Cardiac and arrhythmic complications in patients with COVID-19. J Cardiovasc Electrophysiol. 2020; 31(5): 1003-8. https://dx.doi.org/10.1111/jce.14479
  9. Zheng Y.-Y., Ma Y.-T., Zhang J.-Y., Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5): 259-60. https://dx.doi.org/10.1038/s41569-020-0360-5.
  10. Романов Ю.А. SARS-CoV-2, COVID-19 и сердечно-сосудистые осложнения: взгляд с позиции сосудистого эндотелия. Кардиологический вестник. 2022; 17(1): 21-28. EDN: QFRPKX.
  11. Ungaro R., Sullivan T., Colombel J., Patel G. What should gastroenterologists and patients know about COVID-19? Clin Gastroenterol Hepatol. 2020; 18(7): 1409-11. https://dx.doi.org/10.1016/jxgh.2020.03.020.
  12. Cheung K., Hung I., Chan P. et al. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong cohort: Systematic review and meta-analysis. Gastroenterol. 2020; 159(1): 81-95. https://dx.doi.org/10.1053/j.gastro.2020.03.065.
  13. Lee I.-C., Huo T.-I., Huang Y.-H. Gastrointestinal and liver manifestations in patients with COVID-19. J Chin Med Assoc. 2020; 83(6): 521-23. https://dx.doi.org/10.1097/JCMA.0000000000000319.
  14. Zhang C., Shi L., Wang F. Liver injury in COVID-19: Management and challenges. Lancet Gastroenterol Hepatol. 2020; 5(5): 428-30. https://dx.doi.org/10.1016/S2468-1253(20)30057-1.
  15. Batlle D., Soler M., Sparks M. et al. Acute kidney injury in COVID-19: Emerging evidence of a distinct pathophysiology. J Am Soc Nephrol. 2020; 31(7): 1380-83. https://dx.doi.org/10.1681/ASN.2020040419.
  16. Portoles J., Marques M., Lopez-Sanchez P. et al. Chronic kidney disease and acute kidney injury in the COVID-19 Spanish outbreak. Nephrol Dial Transplant. 2020; 35(8): 1353-61. https://dx.doi.org/10.1093/ndt/gfaa189.
  17. Doher M., De Carvalho F., Scherer P. et al. Acute kidney injury and renal replacement therapy in critically ill COVID-19 patients: Risk factors and outcomes: a single-center experience in Brazil. Blood Purif. 2021; 50(4-5): 520-30. https://dx.doi.org/10.1159/000513425.
  18. Ellul M., Benjamin L., Singh B. et al. Neurological associations of COVID-19. Lancet Neurol. 2020; 19(9): 767-83. https://dx.doi.org/10.1016/S1474-4422(20)30221-0.
  19. Yachou Y., El Idrissi A., Belapasov V., Ait Benali S. Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: Understanding the neurological manifestations in COVID-19 patients. Neurol Sci. 2020; 41(10): 2657-69. https://dx.doi.org/10.1007/s10072-020-04575-3.
  20. Sepehrinezhad A., Shahbazi A., Negah S. COVID-19 virus may have neuroinvasive potential and cause neurological complications: A perspective review. J Neurovirol. 2020; 26(3): 324-29. https://dx.doi.org/10.1007/s13365-020-00851-2.
  21. Baig A.M. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020; 26(5): 499-501. https://dx.doi.org/10.1111/cns.13372.
  22. Pons S., Fodil S., Azoulay E., Zafrani L. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Critical Care. 2020; 24(1): 1-8. https://dx.doi.org/10.1186/s13054-020-03062-7.
  23. Varga Z., Flammer A., Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234): 1417-18. https://dx.doi.org/10.1016/S0140-6736(20)30937-5.
  24. O'Sullivan J.M., Mc Gonagle D., Ward S. et al. Endothelial cells orchestrate COVID-19 coagulopathy. Lancet Haematol. 2020; 7(8): e553-e555. https://dx.doi.org/10.1016/S2352-3026(20)30215-5.
  25. Воробьев П.А., Момот А.П., Зайцев А.А. с соавт. Синдром диссеминированного внутрисосудистого свертывания крови при инфекции COVID-19. Терапия. 2020; 6(5): 25-34. https://dx.doi.org/10.18565/therapy.2020.5.25-34. EDN: REJXJZ.
  26. Okada H., Yoshida S., Hara A. et al. Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection. Microcirculation. 2021; 28(3): e12654. https://dx.doi.org/10.1111/micc.12654.
  27. Li T., Liu X., Zhao Z. et al. Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury in carotid artery model. Oncotarget. 2017; 8(53): 91350-61. https://dx.doi.org/10.18632/oncotarget.20518.
  28. Hoppensteadt D., Fareed J. Pharmacological profile of sulodexide.Int Angiol. 2014; 33(3): 229-35.
  29. Бурячковская Л.И., Мелькумянц А.М., Ломакин Н.В. с соавт. Повреждение сосудистого эндотелия и эритроцитов у больных COVID-19. Consilium Medicum. 2021; 23(6): 469-476. https://dx.doi.org/10.26442/20751753.2021.6.200939. EDN: PUBCZD.
  30. Melkumyants A., Buryachkovskaya L., Lomakin N. et al. Mild COVID-19 and impaired cell-endothelial crosstalk: Considering longterm antithrombotics and vascular protection? Thromb Haemost. 2022; 122(1): 123-30. https://dx.doi.org/10.1055/a-1551-9911.
  31. Dignat-George F., Sampol J. Circulating endothelial cells in vascular disorders: New insights into an old concept. Eur J Haematol. 2000; 65(4): 215-20. https://dx.doi.org/10.1034/j.1600-0609.2000.065004215.x.
  32. Furchgott R.F., Zawadszki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288(5789): 373-76. https://dx.doi.org/10.1038/288373a0.
  33. Мелькумянц А.М., Балашов С.А. Механочувствительность артериального эндотелия. М.: Триада. 2005; 207 с. ISBN: 5-94789-133-6.
  34. Teijaro J., Walsh K., Cahalan S. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell. 2011; 146(6): 980-91. https://dx.doi.org/10.1016/jxell.2011.08.015.
  35. Wang H., Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med. 2008; 26(6): 711-15. https://dx.doi.org/10.1016/j.ajem.2007.10.031.
  36. Alphonsus C.S., Rodseth R.N. The endothelial glycocalyx: A review of the vascular barrier. Anaesthesia. 2014; 69(7): 777-84. https://dx.doi.org/10.1111/anae.12661.
  37. Weinbaum S., Tarbell J.M., Damiano E.R. The structure and function of the endothelial glycocalyx layer. Ann Rev Biomed Eng. 2007; 9: 121-67. https://dx.doi.org/10.1146/annurev.bioeng.9.060906.151959.
  38. Zhang X., Sun D., Song J.W. et al. Endothelial cell dysfunction and glycocalyx - A vicious circle. Matrix Biol. 2018; 71-72: 421-31. https://dx.doi.org/10.1016/j.matbio.2018.01.026.
  39. Frati-Munari A.C. [Medical significance of endothelial glycocalyx. Arch Cardiol Mex. 2013; 83(4): 303-12 (In Spanish)]. https://dx.doi.org/10.1016/j.acmx.2013.04.015.
  40. Becker B.F., Jacob M., Leipert S. et al. Degradation of the endothelial glycocalyx in clinical settings: Searching for the sheddases. Brit J Clin Pharmacol. 2015; 80(3): 389-402. https://dx.doi.org/10.1111/bcp.12629.
  41. Henrich M., Gruss M., Weigand M.A. Sepsis-induced degradation of endothelial glycocalix. Scientif World J. 2010; 10: 917-23. https://dx.doi.org/10.1100/tsw.2010.88.
  42. Yamaoka-Tojo M. Vascular endothelial glycocalyx damage in COVID-19.Internat J Molec Sci. 2020; 21(24): 9712. https://dx.doi.org/10.3390/ijms21249712.
  43. Mattana P., Mannello F., Ferrari P., Agus G.B. Vascular pathologies and inflammation: The anti-inflammatory properties of sulodexide. J Vasc Endovasc Surg. 2012; 19(2): 1-7.
  44. Mannello F., Ligi D., Canale M., Raffetto J.D. Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors from human macrophages: Role of glycosaminoglycans in inflammatory pathways of chronic venous disease. Curr Vasc Pharmacol. 2014; 12(1): 173-85. https://dx.doi.org/10.2174/1570161111666131126144025.
  45. Munari A., Cervera L. Inflammation, metalloproteinases, chronic venous disease and sulodexide. J Cardiovasc Dis Diag. 2015; 3(4): 203. http://dx.doi.org/10.4172/2329-9517.1000203.
  46. Rajtar G., Marchi E., De Gaetano G., Cerletti C. Effects of glycosaminoglycans on platelet and leukocyte function: Role of N-sulfation. Biochem Pharmacol. 1993; 46(5): 958-60. https://dx.doi.org/10.1016/0006-2952(93)90507-S.
  47. Adiguzel C., Iqbal O., Hoppensteadt D. et al.Comparative anticoagulant and platelet modulatory effects of enoxaparin and sulodexide. Clin Appl Thromb Hemost. 2009; 15(5): 501-11. https://dx.doi.org/10.1177/1076029609338711.
  48. Pompilio G., Integlia D., Raffetto J., Palareti G.Comparative efficacy and safety of sulodexide and other extended anticoagulation treatments for prevention of recurrent venous thromboembolism: a Bayesian network meta-analysis. TH Open. 2020; 4(2): e80-e93. https://dx.doi.org/10.1055/s-0040-1709731.
  49. Bikdeli B., Chatterjee S., Kirtane A.J. et al. Sulodexide versus control and the risk of thrombotic and hemorrhagic events: Metaanalysis of randomized trials. Semin Thromb Hemost. 2020; 46(8): 908-18. https://dx.doi.org/10.1055/s-0040-1716874.
  50. Gonzalez-Ochoa A., Raffetto J., Hernandez A. et al. Sulodexide in the treatment of patients with early stages of COVID-19: A randomized controlled trial. Thromb Haemost. 2021; 121(7): 944-54. https://dx.doi.org/10.1055/a-1414-5216.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bionika Media, 2022