ГОРИЗОНТЫ ГЕПАРИНОТЕРАПИИ ПРИ COVID-19 И ЗАБОЛЕВАНИЯХ, СВЯЗАННЫХ С ПАНДЕМИЕЙ
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Ключевые слова

COVID-19
гепарин
комплексообразование
системы крови
противовоспалительные свойства
посттравматическое стрессовое расстройство

Как цитировать

Кондашевская, М. В. (2022). ГОРИЗОНТЫ ГЕПАРИНОТЕРАПИИ ПРИ COVID-19 И ЗАБОЛЕВАНИЯХ, СВЯЗАННЫХ С ПАНДЕМИЕЙ. Российский физиологический журнал им. И. М. Сеченова, 108(4), 399–413. https://doi.org/10.31857/S0869813922040045

Аннотация

Заболевание, распространившееся по всему миру, вызываемое коронавирусом SARS-CoV-2 и названное COVID-19, первоначально считалось острым респираторным дистресс-синдромом (ОРДС). Затем было установлено, что это заболевание характеризуется несвойственными для многих остальных ОРДС тромбозами кровеносных сосудов. Применение в качестве антикоагулянта препаратов нефракционированного и/или низкомолекулярного гепарина значительно снизило смертность и тяжесть течения заболевания, так как гепарин является полифункциональным средством. В представленном обзоре обобщены сведения литературы о механизмах патогенеза SARS-CoV-2, охарактеризованы свойства гепарина, позволяющие ингибировать эти механизмы на любой стадии патологического процесса. Предложена гипотеза формирования порочного патогенетического круга при COVID-19, а также авторский подход к использованию гепарина в малых дозах, за рамками его антикоагулянтных свойств. Проведенный анализ большого спектра эффектов и механизмов действия гепарина поможет создать у заинтересованного читателя представление о современных возможностях применения этого лекарственного препарата.

https://doi.org/10.31857/S0869813922040045
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Литература

Ahmed S, Zimba O, Gasparyan AY (2020) Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow's triad. Clin Rheumatol 39(9): 2529–2543. https://doi.org/10.1007/s10067-020-05275-1

Huang H, Zhang M, Chen C, Zhang H, Wei Y, Tian J, Shang J, Deng Y, Du A, Dai H (2020) Clinical features of patients infected with 2019 novel corona-virus in Wuhan, China. Lancet 395(10223): 497–506. https://doi.org/10.1016/S0140– 6736 (20) 30183–5

Sholzberg M, Tang GH, Negri E, Rahhal H, Kreuziger LB, Pompilio CE, James P, Fralick M, AlHamzah M, Alomran F, Tseng E, Lim G, Lillicrap D, Carrier M, Áinle FN, Beckett A, da Costa BR, Thorpe K, Middeldorp S, Lee A, Cushman M, Jüni P (2021) Coagulopathy of hospitalised COVID-19: A Pragmatic Randomised Controlled Trial of Therapeutic Anticoagulation versus Standard Care as a Rapid Response to the COVID-19 Pandemic (RAPID COVID COAG - RAPID Trial): A structured summary of a study protocol for a randomised controlled trial. Trials 22(1):202. https://doi.org/10.1186/s13063-021-05076-0

World Health Organization (2020) Clinical management of COVID-19. https://www.who.int/publications/i/item/clinical-management-of COVID-19

McLean J (1959) The discovery of heparin. Circulation 19(1):75-78. https://doi.org/10.1161/01.cir.19.1.75

Handin RI (2016) The history of antithrombotic therapy: the discovery of heparin, the vitamin K antagonists, and the utility of aspirin. Hematol Oncol Clin North Am 30(5): 987–993. https://doi.org/10.1016/j.hoc.2016.06.002

Кондашевская МВ (2019) Экосистема тучных клеток – ключевой полифункциональный компонент организма животных и человека. Обзор. М. Группа МДВ. ISBN 978-5906748-08-9 К 64. [Kondashevskaya MV (2019) The ecosystem of mast cells is a key multifunctional component of the body of animals and humans. Review. M. Group MDV. ISBN 978-5906748-08-9 К 64. (In Russ)].

Кондашевская МВ (2021) Гепарин тучных клеток – новые сведения о старом компоненте (обзор). Вестник РАМН 76(2): 149–158. [Kondashevskaya MV (2021) Mast cell heparin – new information on the old component. Review. Bull Russ Acad Med Sci 76 (2): 149-158. (In Russ)].https://doi.org/10.15690/vramn1284

Кондашевская МВ (2010) Современные представления о роли гепарина в гемостазе и регуляции ферментативной и гормональной активности (обзор). Вестник РАМН 7: 35–43. [Kondashevskaya MV (2010) Modern ideas about the role of heparin in hemostasis and regulation of enzymatic and hormonal activity (review). Bull Russ Acad Med Sci 76 (2): 149-158. (In Russ)].

Kudrjashov BA, Pastorova VE, Lyapina LA (1983) Anticoagulating and non-enzymatic fibrinolytic activities of heparin-antithrombin III and antithrombin III-heparin-thrombin complexes in vitro and in vivo. Folia Haematol Int Mag Klin Morphol Blutforsch 110(5): 731–742.

Aláez-Versón CR, Lantero E, Fernàndez-Busquets X (2017) Heparin: new life for an old drug. Nanomedicine (Lond) 12(14): 1727–1744. https://doi.org/10.2217/nnm-2017-0127

Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensinconverting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275(43): 33238–3243. https://doi.org/10.1074/jbc.M002615200

Шатунова ПО, Быков АС, Свитич ОА, Зверев ВВ (2020) Ангиотензинпревращающий фермент 2. Подходы к патогенетической терапии COVID-19. Журн микробиол эпидемиол и иммунобиол 97(4): 339-345. [Shatunova PO, AS Bykov, OA Svitich, VV Zverev (2020) Angiotensin-converting enzyme 2. Approaches to pathogenetic therapy of COVID-19. J Microbiol Epidemiol and Immunobiol 97(4): 339–349. (In Russ)]. https://doi.org/10.36233/0372-9311-2020-97-4-6

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181: 271–280. https://doi.org/10.1016/j.cell.2020.02.052

Belen-Apak FB, Sarialioglu F (2020) The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases? Med Hypotheses 20(142): 109743. https://doi.org/10.1016/j.mehy.2020.109743

Tan CW, Sam IC, Chong WL, Lee VS, Chan YF (2017) Polysulfonatesuramin inhibits Zika virus infection. Antiviral Res 143: 186–194. https://doi.org/10.1016/j.antiviral.2017.04.017

Partridge LJ, Urwin L, Nicklin MJH, James DC, Green LR, Monk PN (2021) ACE2-independent interaction of SARS-CoV-2 spike protein with human epithelial cells is inhibited by unfractionated heparin. Cells 10(6): 1419. https://doi.org/10.3390/cells10061419

Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt ZX, Smith LP, Cheng SS, Overdier KH, Thompson KR, Geraci MW, Douglas IS, Pearse DB, Tuder RM (2012) The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 18: 1217–1223. https://doi.org/10.1038/nm.2843

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 383(2): 120–128. https://doi.org/10.1056/NEJMoa2015432

Kanthi Y, Knight JS, Zuo Y, Pinsky DJ (2020) New (re)purpose for an old drug: purinergic modulation may extinguish the COVID-19 thromboinflammatory firestorm. JCI Insight 5(14): e140971. https://doi.org/10.1172/jci.insight.140971

Vojacek JF (2017) Should we replace the terms intrinsic and extrinsic coagulation pathways with tissue factor pathway? Clin Appl Thromb Hemost 23(8): 922–927. https://doi.org/10.1177/1076029616673733

Obergan TYu, Lyapina LA, PastorovaVE (2007) Antithrombotic activity of heparin-ATP complex. Bull Exp Biol Med. 143(3): 299–301. https://doi.org/10.1007/s10517-007-0094-y

Ghosh TK , Eis PS, Mullaney JM, Ebert CL, Gill DL (1988) Competitive, reversible, and potent antagonism of inositol 1,4,5-trisphosphate-activated calcium release by heparin. J Biol Chem 263(23):11075–11079.

Pletcher CH, Cunningham MT, Nelsestuen GL (1986) Molecular weight analysis of antithrombin III-heparin and antithrombin III-thrombin-heparin complexes. J Biol Chem 261(9): 4143–4147.

Meyer D, Tsakiris DA, Marbet GA (1989) Thrombin-antithrombin III complexes as a measure of effective heparin treatment? Schweiz Med Wochenschr 119(39): 1352–1354.

Kudrjashov BA, Liapina LA, Uljanov AM (1978) Complex fibrinogen-heparin (FH) and fibrinogen degradation products (FDP) in blood of rats after intravenous injection of thrombin. Thromb Res 13(3): 397–407.

Ji H-L, Zhao R, Matalon S, Matthay MA (2020) Elevated plasmin(ogen) as a common risk factor for COVID-19 susceptibility Physiol Rev 100(3): 1065–1075. https://doi.org/10.1152/physrev.00013.2020

Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ (2020) Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. J Thromb Haemost 18(7): 1548–1555. https://doi.org/10.1111/jth.14872

Antoniak S (2018) The coagulation system in host defense. Res Pract Thromb Haemost 2(3): 549–557. https://doi.org/10.1002/rth2.12109

Ong WY, Go ML, Wang DY, Cheah IK, Halliwell B (2021) Effects of antimalarial drugs on neuroinflammation-potential use for treatment of COVID-19-related neurologic complications. Mol Neurobiol 58(1): 106–117. https://doi.org/10.1007/s12035-020-02093-z

Hogwood J, Pitchford S, Mulloy B, Page C, Gray E (2020) Heparin and non-anticoagulant heparin attenuate histone-induced inflammatory responses in whole blood. PLoS One 15(5):e0233644. https://doi.org/10.1371/journal.pone.0233644

Fernandes IG, de Brito CA, Dos Reis VMS, Sato MN, Pereira NZ (2020) SARS-CoV-2 and other respiratory viruses: what does oxidative stress have to do with it? Oxid Med Cell Longev 2020:8844280. https://doi.org/10.1155/2020/8844280

Onishi JC, Häggblom MM, Shapses SA (2020) Can dietary fatty acids affect the COVID-19 infection outcome in vulnerable populations? mBio 11(4e): 01723-20. https://doi.org/10.1128/mBio.01723-20

Assimakopoulos SF, Mastronikolis S, DE Lastic AL, Aretha D, Papageorgiou D, Chalkidi T, Oikonomou I, Triantos C, Mouzaki A, Marangos M (2021) Intestinal Barrier Biomarker ZO1 and Endotoxin Are Increased in Blood of Patients With COVID-19-associated Pneumonia. In Vivo 35(4):2483–2488. https://doi.org/10.21873/invivo.12528

Li LF, Liu YY, Lin SW, Chang CH, Chen NH, Hung CY, Lee CS (2020) Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model. Int J Mol Sci 21(9):3097. https://doi.org/10.3390/ijms21093097

Domínguez-Salas S, Gómez-Salgado J, Andrés-Villas M, Díaz-Milanés D, Romero-Martín M, Ruiz-Frutos C (2020) Psycho-Emotional Approach to the Psychological Distress Related to the COVID-19 Pandemic in Spain: A Cross-Sectional Observational Study. Healthcare (Basel) 8(3): E190. https://doi.org/10.3390/healthcare8030190

Kondashevskaya MV (2018) Experimental evaluation of the effects of low-dose heparin on the behavior and morphofunctional status of the liver in Wistar rats with posttraumatic stress disorders. Bull Exp Biol Med 164(10): 490–494. https://doi.org/10.1007/s10517-018–4018–9

Кудряшов БА, Шапиро ФБ, Ломовская ЕГ, Ляпина ЛА (1975) Роль адреналина и АКТГ в процессе образования комплексных соединений в крови при иммобилизационном стрессе. Пробл эндокринол 21(5):54–59. [Kudriashov BA, Shapiro FB, Lomovskaia EG, Liapina LA (1975) The role of adrenaline and ACTH in the process of complex heparin compound formation in the blood during imobilization stress. Probl Endokrinol (Mosk) 21(5):54–59. (In Russ)].

Ляпина ЛА, Кондашевская МВ, Зиадетдинова ГА, Успенская МС (2000) Сравнительное исследование антикоагулянтов из различных экстрактов Paeonia anomala. Изв Акад наук Сер биол. (3):345-349. [Lyapina LA, Kondashevskaya MV, Ziadetdinova GA, Uspenskaya MS (2000) Comparative study of anticoagulants from various extracts of Paeonia anomala. Izv Akad Nauk Ser Biol (3):345–349. (In Russ)].