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Semin Thromb Hemost 2014; 40(08): 831-836
DOI: 10.1055/s-0034-1395152
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Glycosaminoglycans: Anticoagulant and Nonanticoagulant Actions: A Short History of Symposia Held at Villa Vigoni[*]

Job Harenberg
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
,
Benito Casu
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
,
Roland Krämer
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
,
Giangiacomo Torri
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
,
Annamaria Naggi
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
,
Sandra Krämer
1   Clinical Pharmacology, Faculty of Medicine Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
06 November 2014 (online)

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Abstract

Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans, was discovered in the beginning of the 20th century and was initially identified as a procoagulant isolated from liver tissue. After the first application in patients approximately 30 years later, further purification identified the major as well as minor, but important, component units of the complex chain mixtures constituting heparin and the multiplex actions became a scientific challenge recently. A series of “Glycosaminoglycan symposium—anticoagulant and nonanticoagulant actions” developed over the past 20 years and focused on this topic has published research data in three issues of Seminars in Thrombosis & Hemostasis and in several other international scientific journals. The latest developments on the methods of analysis, the synthesis, the degradation by heparanases and the nonanticoagulant effects in tumor growth, in anti-inflammatory diseases, and in Alzheimer diseases as presented in the 21st symposium are summarized in the present overview on the occasion of the 40th anniversary of the journal with special reference to the journal's founding Editor in Chief, Eberhard F. Mammen.

Keywords

glycosaminoglycans - heparin - low-molecular-weight heparin - thromboembolism - nonanticoagulant effects

* Dedicated on the 40th anniversary of Seminars in Thrombosis & Hemostasis to Eberhard F. Mammen, Founding Editor and Editor-in-Chief of this journal until 2008.


 

  • References

  • 1 Schmidt-Mülheim A. Beiträge zur Kenntnis des Peptons und seiner physiologischen Bedeutung. Vereinigung Wissenschaftlicher Verlage: Germany; 1880: 33-56
    Google Scholar
  • 2 McLean J. The thromboplastic action of cephalin. Am J Physiol 1916; 41: 250-257
    PubMedGoogle Scholar
  • 3 Howell WH, Holt E. Two new factors in blood coagulation - heparin and prothrombin. Am J Physiol 1918; 47: 328-341
    PubMedGoogle Scholar
  • 4 Howell WH, McDonald CH. Note on the effect of repeated intravascular injections of heparin. John Hopkins Hospital 1930; 46: 365-371
    PubMedGoogle Scholar
  • 5 Beller FK, Mammen E. Studies on a third plasma factor in thromboplastin formation [in German]. Klin Wochenschr 1955; 33 (7-8) 155-156
    CrossrefPubMedGoogle Scholar
  • 6 Nieth H, Mammen E, Gross R. Heparinization of blood in extracorporeal hemodialysis [in German]. Klin Wochenschr 1958; 36 (8) 372-376
    CrossrefPubMedGoogle Scholar
  • 7 Troy S, Fruncillo R, Ozawa T, Mammen E, Holloway S, Chiang S. The dose proportionality of the pharmacokinetics of ardeparin, a low molecular weight heparin, in healthy volunteers. J Clin Pharmacol 1995; 35 (12) 1194-1199
    CrossrefPubMedGoogle Scholar
  • 8 Mammen EF. Why low molecular weight heparin?. Semin Thromb Hemost 1990; 16 (Suppl): 1-4
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Harenberg J, Casu B. Glycosaminoglycans I. Semin Thromb Hemost 1994; 20: 133-222
    PubMedGoogle Scholar
  • 10 Harenberg J, Casu B. Glycosaminoglycans: anticoagulant and nonanticoagulant actions. Semin Thromb Hemost 2002; 28: 323-402
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Harenberg J, Casu B (Guest Editors). New anticoagulants. [Complete Issue]. Semin Thromb Hemost 2007; 33 (5) 449-562
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Beeler D, Rosenberg R, Jordan R. Fractionation of low molecular weight heparin species and their interaction with antithrombin. J Biol Chem 1979; 254 (8) 2902-2913
    PubMedGoogle Scholar
  • 13 Petitou M, Duchaussoy P, Herbert JM , et al. The synthetic pentasaccharide fondaparinux: first in the class of antithrombotic agents that selectively inhibit coagulation factor Xa. Semin Thromb Hemost 2002; 28 (4) 393-402
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Viskov C, Elli S, Urso E , et al. Heparin dodecasaccharide containing two antithrombin-binding pentasaccharides: structural features and biological properties. J Biol Chem 2013; 288 (36) 25895-25907
    CrossrefPubMedGoogle Scholar
  • 15 Malsch R, Harenberg J. High-performance size exclusion chromatography and polyacrylamide gel electrophoresis for characterization of unfractionated and low molecular mass glycosaminoglycans. Semin Thromb Hemost 1994; 20 (2) 135-143
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Ucakturk E, Cai C, Li L, Li G, Zhang F, Linhardt RJ. Capillary electrophoresis for total glycosaminoglycan analysis. Anal Bioanal Chem 2014; 406 (19) 4617-4626
    CrossrefPubMedGoogle Scholar
  • 17 Dinges MM, Solakyildirim K, Larive CK. Affinity capillary electrophoresis for the determination of binding affinities for low molecular weight heparins and antithrombin-III. Electrophoresis 2014; 35 (10) 1469-1477
    CrossrefPubMedGoogle Scholar
  • 18 Rudd TR, Skidmore MA, Guimond SE , et al. Glycosaminoglycan origin and structure revealed by multivariate analysis of NMR and CD spectra. Glycobiology 2009; 19 (1) 52-67
    CrossrefPubMedGoogle Scholar
  • 19 Sturiale L, Naggi A, Torri G. MALDI mass spectrometry as a tool for characterizing glycosaminoglycan oligosaccharides and their interaction with proteins. Semin Thromb Hemost 2001; 27 (5) 465-472
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Bultel L, Landoni M, Grand E, Couto AS, Kovensky J. UV-MALDI-TOF mass spectrometry analysis of heparin oligosaccharides obtained by nitrous acid controlled degradation and high performance anion exchange chromatography. J Am Soc Mass Spectrom 2010; 21 (1) 178-190
    CrossrefPubMedGoogle Scholar
  • 21 Ratnoff OD, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med 1951; 37 (2) 316-320
    PubMedGoogle Scholar
  • 22 O'Connor SD, Taylor AJ, Williams EC, Winter TC. Coagulation concepts update. AJR Am J Roentgenol 2009; 193 (6) 1656-1664
    CrossrefPubMedGoogle Scholar
  • 23 Favaloro EJ, Lippi G, Koutts J. Laboratory testing of anticoagulants: the present and the future. Pathology 2011; 43 (7) 682-692
    CrossrefPubMedGoogle Scholar
  • 24 Harenberg J, Giese C, Hagedorn A, Traeger I, Fenyvesi T. Determination of antithrombin-dependent factor Xa inhibitors by prothrombin-induced clotting time. Semin Thromb Hemost 2007; 33 (5) 503-507
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Alban S. Adverse effects of heparin. Handbook Exp Pharmacol 2012; (207) 211-263
    PubMedGoogle Scholar
  • 26 Szelke H, Harenberg J, Krämer R. Detection and neutralisation of heparin by a fluorescent ruthenium compound. Thromb Haemost 2009; 102 (5) 859-864
    PubMedGoogle Scholar
  • 27 Szelke H, Schübel S, Harenberg J, Krämer R. Interaction of heparin with cationic molecular probes: probe charge is a major determinant of binding stoichiometry and affinity. Bioorg Med Chem Lett 2010; 20 (4) 1445-1447
    CrossrefPubMedGoogle Scholar
  • 28 Szelke H, Schübel S, Harenberg J, Krämer R. A fluorescent probe for the quantification of heparin in clinical samples with minimal matrix interference. Chem Commun (Camb) 2010; 46 (10) 1667-1669
    CrossrefPubMedGoogle Scholar
  • 29 Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med 2004; 164 (1) 17-26
    CrossrefPubMedGoogle Scholar
  • 30 Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med 2013; 126 (9) e13-e21
    PubMedGoogle Scholar
  • 31 Crafoord C. Heparin and post-operative thrombosis. Acta Chir Scand 1939; 82: 319-335
    PubMedGoogle Scholar
  • 32 McLean J. The discovery of heparin. Circulation 1959; 19 (1) 75-78
    CrossrefPubMedGoogle Scholar
  • 33 Wells PS, Forgie MA, Rodger MA. Treatment of venous thromboembolism. JAMA 2014; 311 (7) 717-728
    CrossrefPubMedGoogle Scholar
  • 34 Kearon C, Akl EA, Comerota AJ , et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e419S-e494S
    CrossrefPubMedGoogle Scholar
  • 35 Kearon C. A conceptual framework for two phases of anticoagulant treatment of venous thromboembolism. J Thromb Haemost 2012; 10 (4) 507-511
    CrossrefPubMedGoogle Scholar
  • 36 Bhutia S, Wong PF. Once versus twice daily low molecular weight heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev 2013; 7: CD003074
    PubMedGoogle Scholar
  • 37 Che DH, Cao JY, Shang LH, Man YC, Yu Y. The efficacy and safety of low-molecular-weight heparin use for cancer treatment: a meta-analysis. Eur J Intern Med 2013; 24 (5) 433-439
    CrossrefPubMedGoogle Scholar
  • 38 Girolami A, Treleani M, Bonamigo E, Tasinato V, Girolami B. Venous thrombosis in rare or unusual sites: a diagnostic challenge. Semin Thromb Hemost 2014; 40 (1) 81-87
    PubMedGoogle Scholar
  • 39 Harenberg J. Development of new anticoagulants: present and future. Semin Thromb Hemost 2008; 34 (8) 779-793
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Malsch R, Harenberg J, Guerrini M, Torri G, Casu B, Heene DL. Semisynthesis and analysis of lipophilically modified unfractionated and low molecular mass heparins. Semin Thromb Hemost 1994; 20 (2) 182-192
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Piazolo L, Harenberg J, Malsch R, Heene DL. Binding of fluorescent-labeled low molecular mass heparin to latex microspheres and to rat and human leukocytes. Semin Thromb Hemost 1994; 20 (3) 227-235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Harenberg J, Casu B, Guerrini M , et al. Low-molecular-weight heparin and dermatan sulfate end group-labeled with tyramine and fluorescein. Biochemical and biological characterization of the fluorescent-labeled heparin derivative. Semin Thromb Hemost 2002; 28 (4) 343-354
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Mietzsch M, Broecker F, Reinhardt A, Seeberger PH, Heilbronn R. Differential adeno-associated virus serotype-specific interaction patterns with synthetic heparins and other glycans. J Virol 2014; 88 (5) 2991-3003
    CrossrefPubMedGoogle Scholar
  • 44 Alekseeva A, Casu B, Torri G, Pierro S, Naggi A. Profiling glycol-split heparins by high-performance liquid chromatography/mass spectrometry analysis of their heparinase-generated oligosaccharides. Anal Biochem 2013; 434 (1) 112-122
    CrossrefPubMedGoogle Scholar
  • 45 Poli M, Asperti M, Naggi A , et al. Glycol-split nonanticoagulant heparins are inhibitors of hepcidin expression in vitro and in vivo. Blood 2014; 123 (10) 1564-1573
    CrossrefPubMedGoogle Scholar
  • 46 Sudha T, Phillips P, Kanaan C, Linhardt RJ, Borsig L, Mousa SA. Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model. Clin Exp Metastasis 2012; 29 (5) 431-439
    CrossrefPubMedGoogle Scholar
  • 47 Schlesinger M, Schmitz P, Zeisig R , et al. The inhibition of the integrin VLA-4 in MV3 melanoma cell binding by non-anticoagulant heparin derivatives. Thromb Res 2012; 129 (5) 603-610
    CrossrefPubMedGoogle Scholar
  • 48 Gasimli L, Glass CA, Datta P , et al. Bioengineering murine mastocytoma cells to produce anticoagulant heparin. Glycobiology 2014; 24 (3) 272-280
    CrossrefPubMedGoogle Scholar
  • 49 Johnstone KD, Karoli T, Liu L , et al. Synthesis and biological evaluation of polysulfated oligosaccharide glycosides as inhibitors of angiogenesis and tumor growth. J Med Chem 2010; 53 (4) 1686-1699
    CrossrefPubMedGoogle Scholar
  • 50 Christianson HC, Svensson KJ, van Kuppevelt TH, Li JP, Belting M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA 2013; 110 (43) 17380-17385
    CrossrefPubMedGoogle Scholar
  • 51 Nadir Y, Brenner B. Heparanase multiple effects in cancer. Thromb Res 2014; 133 (Suppl. 02) S90-S94
    PubMedGoogle Scholar
  • 52 Vlodavsky I, Iozzo RV, Sanderson RD. Heparanase: multiple functions in inflammation, diabetes and atherosclerosis. Matrix Biol 2013; 32 (5) 220-222
    CrossrefPubMedGoogle Scholar
  • 53 Schwörer R, Zubkova OV, Turnbull JE, Tyler PC. Synthesis of a targeted library of heparan sulfate hexa- to dodecasaccharides as inhibitors of β-secretase: potential therapeutics for Alzheimer's disease. Chemistry 2013; 19 (21) 6817-6823
    CrossrefPubMedGoogle Scholar