Rhamnan sulfate extracted from Monostroma nitidum attenuates blood coagulation and inflammation of vascular endothelial cells

Abstract

Rhamnan sulfate (RS) is a polysaccharide with a rhamnose backbone isolated from Monostroma nitidum. Like heparin, it exerts anticoagulant activity in the presence of antithrombin. Endothelial cells facilitate the crosstalk between blood coagulation and vascular inflammation. In this study, we compared the effect of RS with that of heparin on blood coagulation and vascular endothelial cells in the presence or absence of inflammatory factors, using human umbilical vein endothelial cells. We found that RS significantly enhances inhibition of thrombin and factor Xa in the presence of antithrombin as well as heparin, and that RS inhibits tissue factor expression and von Willebrand factor release from the endothelial cells treated with or without lipopolysaccharide, tumor necrosis factor-α, or thrombin. Heparin did not show any effects on endothelial cell inflammation. Our findings suggest that RS, like heparin, is an antithrombin-dependent anticoagulant and, unlike heparin, is a potent anti-inflammatory agent acting on vascular endothelial cells.

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Abbreviations

APTT:

Activated partial thromboplastin time

HUVEC:

Human umbilical vein endothelial cells

LPS:

Lipopolysaccharide

PT:

Prothrombin time

RS:

Rhamnan sulfate

TF:

Tissue factor

TNF:

Tumor necrosis factor

VWF:

Von Willebrand factor

References

  1. 1.

    Zang L, Shimada Y, Tanaka T, Nishimura N (2015) Rhamnan sulphate from Monostroma nitidum attenuates hepatic steatosis by suppressing lipogenesis in a diet-induced obesity zebrafish model. J Funct Foods 17:364–370. https://doi.org/10.1016/j.jff.2015.05.041

    CAS  Article  Google Scholar 

  2. 2.

    Harada N, Maeda M (1998) Chemical structure of antithrombin-active Rhamnan sulfate from Monostrom nitidum. Biosci Biotechnol Biochem 62:1647–1652. https://doi.org/10.1271/bbb.62.1647

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Lee JB, Koizumi S, Hayashi K, Hayashi T (2010) Structure of rhamnan sulfate from the green alga Monostroma nitidum and its anti-herpetic effect. Carbohydr Polym 81:572–577. https://doi.org/10.1016/j.carbpol.2010.03.014

    CAS  Article  Google Scholar 

  4. 4.

    Tako M, Yamashiro Y, Teruya T, Uechi S (2017) Structure-function relationship of rhamnan sulfate isolated from commercially cultured edible green seaweed, Monostroma nitidum. Am J Appl Chem 5:38–44. https://doi.org/10.11648/j.ajac.20170502.13

    CAS  Article  Google Scholar 

  5. 5.

    Li H, Mao W, Hou Y, Gao Y, Qi X, Zhao C, Chen Y, Chen Y, Li N, Wang C (2012) Preparation, structure and anticoagulant activity of a low molecular weight fraction produced by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum. Bioresour Technol 114:414–418. https://doi.org/10.1016/j.biortech.2012.03.025

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Yamashiro Y, Nakamura M, Yogi T, Teruya T, Konishi T, Uechi S, Tako M (2017) Anticoagulant activity of rhamnan sulfate isolated from commercially cultured Monostroma nitidum. Int J Biomed Mater Res 5:37–43. https://doi.org/10.11648/j.ijbmr.20170503.12

    Article  Google Scholar 

  7. 7.

    Lee JB, Hayashi K, Hayashi T, Sankawa U, Maeda M (1999) Antiviral activities against HSV-1, HCMV, and HIV-1 of rhamnan sulfate from Monostroma latissimum. Planta Med 65:439–441. https://doi.org/10.1055/s-2006-960804

    Article  PubMed  Google Scholar 

  8. 8.

    Lee JB, Hayashi K, Maeda M, Hayashi T (2004) Antiherpetic activities of sulfated polysaccharides from green algae. Planta Med 70:813–817. https://doi.org/10.1055/s-2004-827228

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561

    CAS  PubMed  Google Scholar 

  10. 10.

    Sadler JE (1998) Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 67:395–424. https://doi.org/10.1146/annurev.biochem.67.1.395

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Noone DG, Riedl M, Licht C (2018) The role of von Willebrand factor in thrombotic microangiopathy. Pediatr Nephrol 33:1297–1307. https://doi.org/10.1007/s00467-017-3744-y

    Article  PubMed  Google Scholar 

  12. 12.

    Björk I, Lindahl U (1982) Mechanism of the anticoagulant action of heparin. Mol Cell Biochem 48:161–182. https://doi.org/10.1007/BF00421226

    Article  PubMed  Google Scholar 

  13. 13.

    Chuang YJ, Swanson R, Raja SM, Olson ST (2001) Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence. Evidence for an exosite determinant of factor Xa specificity in heparin-activated antithrombin. J Biol Chem 276:14961–14971. https://doi.org/10.1074/jbc.M011550200

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Li N, Liu X, He X, Wang S, Cao S, Xia Z, Xian H, Qin L, Mao W (2017) Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava. Carbohydr Polym 159:195–206. https://doi.org/10.1016/j.carbpol.2016.12.013

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Liu X, Du P, Liu X, Cao S, Qin L, He M, He X, Mao W (2018) Anticoagulant properties of a green algal rhamnan-type sulfated polysaccharide and its low-molecular-weight fragments prepared by mild acid degradation. Mar Drugs. https://doi.org/10.3390/md16110445

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Liu X, Wang S, Cao S, He X, Qin L, He M, Yang Y, Hao J, Mao W (2018) Structural characteristics and anticoagulant property in vitro and in vivo of a seaweed sulfated rhamnan. Mar Drugs. https://doi.org/10.3390/md16070243

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Nemerson Y (1988) Tissue factor and hemostasis. Blood 71:1–8

    CAS  Article  Google Scholar 

  18. 18.

    Wada H, Wakita Y, Shiku H (1995) Tissue factor expression in endothelial cells in health and disease. Blood Coagul Fibrinolysis 6(1):S26–S31

    CAS  Article  Google Scholar 

  19. 19.

    Esmon CT (2003) Inflammation and thrombosis. J Thromb Haemost 1:1343–1348

    CAS  Article  Google Scholar 

  20. 20.

    Schneppenheim R, Budde U (2011) von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein. J Thromb Haemost 9(Suppl 1):209–215. https://doi.org/10.1111/j.1538-7836.2011.04324.x

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Yau JW, Teoh H, Verma S (2015) Endothelial cell control of thrombosis. BMC Cardiovasc Disord 15:130. https://doi.org/10.1186/s12872-015-0124-z

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Kolarova H, Ambruzova B, Svihalkova Sindlerova L, Klinke A, Kubala L (2014) Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm 2014:694312. https://doi.org/10.1155/2014/694312

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, Oude Egbrink MG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454:345–359. https://doi.org/10.1007/s00424-007-0212-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    van den Berg BM, Vink H, Spaan JA (2003) The endothelial glycocalyx protects against myocardial edema. Circ Res 92:592–594. https://doi.org/10.1161/01.Res.0000065917.53950.75

    Article  PubMed  Google Scholar 

  25. 25.

    Morita T, Kato H, Iwanaga S, Takada K, Kimura T (1977) New fluorogenic substrates for alpha-thrombin, factor Xa, kallikreins, and urokinase. J Biochem 82:1495–1498

    CAS  Article  Google Scholar 

  26. 26.

    Okamoto T, Akita N, Nagai M, Hayashi T, Suzuki K (2014) 6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion. J Nat Med 68:144–153. https://doi.org/10.1007/s11418-013-0784-x

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant-in-Aid for challenging Exploratory Research (Grant number 18659280), a Grant-in-Aid for Scientific Research (B) (Grant number 21309292), and a Grant-in-Aid for Scientific Research (C) (Grant numbers 25460396 and 16K08633) from the Japan Society for the Promotion of Science.

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Correspondence to Koji Suzuki.

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This study was performed as a collaborative investigation funded by the Konan Chemical Manufacturing Co. Ltd. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.

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Okamoto, T., Akita, N., Terasawa, M. et al. Rhamnan sulfate extracted from Monostroma nitidum attenuates blood coagulation and inflammation of vascular endothelial cells. J Nat Med 73, 614–619 (2019). https://doi.org/10.1007/s11418-019-01289-5

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Keywords

  • Monostroma nitidum
  • Seaweed
  • Rhamnan sulfate
  • Anti-coagulation
  • Anti-inflammation
  • Vascular endothelium