Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection

Nature Communications

Volumn 7, Issue , 2016, Pages

  Labberton, Linda ^a,b   Kenne, Ellinor ^b   Long, Andy T ^a   Nickel, Katrin F ^a,b   Di Gennaro, Antonio ^b   Rigg, Rachel A ^b,c   Hernandez, James S ^d   Butler, Lynn ^a,b   Maas, Coen ^e   Stavrou, Evi X ^f,g   Renné, Thomas ^a,b  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b KAROLINSKA INSTITUTE   (Sweden)

^c Oregon Health and Science University Department of Biomedical Engineering   (United States)

^d MAYO CLINIC   (United States)

^e UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^f VETERANS AFFAIRS MEDICAL CENTER   (United States)

^g CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 12; FIBRIN; NUCLEIC ACID; POLYPHOSPHATE; RECOMBINANT ENZYME; RECOMBINANT EXOPOLYPHOSPHATASE; THROMBIN; THROMBOPLASTIN; UNCLASSIFIED DRUG; ACID ANHYDRIDE HYDROLASE; BLOOD CLOTTING FACTOR; EXOPOLYPHOSPHATASE; PROTEIN BINDING;

CHEMICAL BINDING; COLIFORM BACTERIUM; GENETIC ANALYSIS; INHIBITOR; INJURY; INORGANIC COMPOUND; PHOSPHATE; POLYMER; TUMOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTICLE; BLEEDING TENDENCY; BLOOD CLOTTING FACTOR 12 DEFICIENCY; BLOOD FLOW; CONTROLLED STUDY; DOSE RESPONSE; DRUG BINDING; DRUG SAFETY; DRUG TARGETING; ENZYME DEGRADATION; FEMALE; IN VIVO STUDY; LUNG EMBOLISM; MALE; MOUSE; NONHUMAN; PROTEIN DOMAIN; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOSIS PREVENTION; VENOUS THROMBOEMBOLISM; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECT; ESCHERICHIA COLI; GENE DELETION; GENETICS; HUMAN; METABOLISM; MUTATION; THROMBOSIS;

ANIMALIA; ESCHERICHIA COLI; MUS;

ACID ANHYDRIDE HYDROLASES; ANIMALS; BLOOD COAGULATION FACTORS; ESCHERICHIA COLI; FACTOR XII; FEMALE; GENE DELETION; HUMANS; MICE; MUTATION; PLATELET AGGREGATION; POLYPHOSPHATES; PROTEIN BINDING; PROTEIN DOMAINS; THROMBIN; THROMBOSIS;

EID: 84986557913     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms12616     Document Type: Article

References (70)

1. Mackman, N. Triggers targets and treatments for thrombosis. Nature 451, 914-918 (2008).
2. Eikelboom, J. W. & Weitz, J. I. New anticoagulants. Circulation 121, 1523-1532 (2010).
3. Franchini, M., Mengoli, C., Cruciani, M., Bonfanti, C. & Mannucci, P. M. Effects on bleeding complications of pharmacogenetic testing for initial dosing of vitamin K antagonists: a systematic review and meta-analysis. J. Thromb. Haemost. 12, 1480-1487 (2014).
4. Baber, U., Mastoris, I. & Mehran, R. Balancing ischaemia and bleeding risks with novel oral anticoagulants. Nat. Rev. Cardiol. 11, 693-703 (2014).
5. Kornberg, A., Rao, N. N. & Ault-Riche, D. Inorganic polyphosphate: a molecule of many functions. Annu. Rev. Biochem. 68, 89-125 (1999).
6. Rao, N. N., Gomez-Garcia, M. R. & Kornberg, A. Inorganic polyphosphate: essential for growth and survival. Annu. Rev. Biochem. 78, 605-647 (2009).
7. Muller, F. et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139, 1143-1156 (2009).
8. Smith, S. A. et al. Polyphosphate modulates blood coagulation and fibrinolysis. Proc. Natl Acad. Sci. USA 103, 903-908 (2006).
9. Puy, C. et al. Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. J. Thromb. Haemost. 11, 1341-1352 (2013).
10. Choi, S. H., Smith, S. A. & Morrissey, J. H. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood 118, 6963-6970 (2011).
11. Choi, S. H., Smith, S. A. & Morrissey, J. H. Polyphosphate accelerates factor V activation by factor XIa. Thromb. Haemost. 113, 599-604 (2014).
12. Smith, S. A. & Morrissey, J. H. Polyphosphate enhances fibrin clot structure. Blood 112, 2810-2816 (2008).
13. Mutch, N. J., Engel, R., Uitte De Willige, S., Philippou, H. & Ariens, R. A. Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. Blood 115, 3980-3988 (2010).
14. Smith, S. A. et al. Polyphosphate exerts differential effects on blood clotting, depending on polymer size. Blood 116, 4353-4359 (2010).
15. Donovan, A. J., Kalkowski, J., Smith, S. A., Morrissey, J. H. & Liu, Y. Size-controlled synthesis of granular polyphosphate nanoparticles at physiologic salt concentrations for blood clotting. Biomacromolecules 15, 3976-3984 (2014).
16. Akiyama, M., Crooke, E. & Kornberg, A. An exopolyphosphatase ofEscherichia coli the enzyme and its ppx gene in a polyphosphate operon. J. Biol. Chem. 268, 633-639 (1993).
17. Rangarajan, E. S. et al. The structure of the exopolyphosphatase (PPX) from Escherichia coli O157: H7 suggests a binding mode for long polyphosphate chains. J. Mol. Biol. 359, 1249-1260 (2006).
18. Bolesch, D. G. & Keasling, J. D. Polyphosphate binding and chain length recognition of Escherichia coli exopolyphosphatase. J. Biol. Chem. 275, 33814-33819 (2000).
19. Choi, S. H. et al. Phosphoramidate end labeling of inorganic polyphosphates: facile manipulation of polyphosphate for investigating and modulating its biological activities. Biochemistry 49, 9935-9941 (2010).
20. Oschatz, C. et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 34, 258-268 (2011).
21. Kishimoto, T. K. et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N. Engl. J. Med. 358, 2457-2467 (2008).
22. Lichko, L. P., Kulakovskaya, T. V. & Kulaev, I. S. Purification and characterization of a soluble polyphosphatase from mitochondria of Saccharomyces cerevisiae. Biochemistry (Mosc) 65, 355-360 (2000).
23. Kannemeier, C. et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc. Natl Acad. Sci. USA 104, 6388-6393 (2007).
24. Larsson, M. et al. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci. Transl. Med. 6, 222ra217 (2014).
25. Stavrou, E. X. et al. Reduced thrombosis in Klkb1-/- mice is mediated by increased Mas receptor, prostacyclin, Sirt1 and KLF4 and decreased tissue factor. Blood 4, 710-719 (2014).
26. Renne, T. et al. Defective thrombus formation in mice lacking coagulation factor XII. J. Exp. Med. 202, 271-281 (2005).
27. Hoffman, M. & Monroe, 3rd D. M. A cell-based model of hemostasis. Thromb. Haemost. 85, 958-965 (2001).
28. Long, A. T., Kenne, E., Jung, R., Fuchs, T. A. & Renne, T. Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J. Thromb. Haemost. 14, 427-437 (2016).
29. Pauer, H. U. et al. Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo. Thromb. Haemost. 92, 503-508 (2004).
30. Ratnoff, O. D. & Colopy, J. E. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J. Clin. Invest. 34, 602-613 (1955).
31. Matafonov, A. et al. Factor XII inhibition reduces thrombus formation in a primate thrombosis model. Blood 123, 1739-1746 (2014).
32. Yau, J. W. et al. Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits. Blood 123, 2102-2107 (2014).
33. Kleinschnitz, C. et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J. Exp. Med. 203, 513-518 (2006).
34. Smith, S. A. & Morrissey, J. H. Polyphosphate as a general procoagulant agent. J. Thromb. Haemost. 6, 1750-1756 (2008).
35. Zhu, S., Travers, R. J., Morrissey, J. H. & Diamond, S. L. FXIa and platelet polyphosphate as therapeutic targets during human blood clotting on collagen/tissue factor surfaces under flow. Blood 126, 1494-1502 (2015).
36. Lorenz, B., Leuck, J., Kohl, D., Muller, W. E. & Schroder, H. C. Anti-HIV-1 activity of inorganic polyphosphates. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 14, 110-118 (1997).
37. Lomashvili, K. A., Khawandi, W. & O'Neill, W. C. Reduced plasma pyrophosphate levels in hemodialysis patients. J. Am. Soc. Nephrol. 16, 2495-2500 (2005).
38. McNicol, A. & Israels, S. J. Platelet dense granules: structure, function and implications for haemostasis. Thromb. Res. 95, 1-18 (1999).
39. Nickel, K. F. et al. The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis. Blood 126, 1379-1389 (2015).
40. Ang, A. L., Kuperan, P., Ng, C. H. & Ng, H. J. Acquired factor V inhibitor. A problem-based systematic review. Thromb. Haemost. 101, 852-859 (2009).
41. Maroney, S. A. & Mast, A. E. New insights into the biology of tissue factor pathway inhibitor. J. Thromb. Haemost. 13(Suppl 1): S200-S207 (2015).
42. Casini, A. et al. Fibrin clot structure in patients with congenital dysfibrinogenaemia. Thromb. Res. 137, 189-195 (2016).
43. Ruiz, F. A., Lea, C. R., Oldfield, E. & Docampo, R. Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J. Biol. Chem. 279, 44250-44257 (2004).
44. Ghosh, S. et al. Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels. Blood 122, 1478-1486 (2013).
45. Corash, L. & Levin, J. The relationship between megakaryocyte ploidy and platelet volume in normal and thrombocytopenic C3H mice. Exp. Hematol 18, 985-989 (1990).
46. Momeni, A. & Filiaggi, M. J. Comprehensive study of the chelation and coacervation of alkaline earth metals in the presence of sodium polyphosphate solution. Langmuir 30, 5256-5266 (2014).
47. Szymusiak, M. et al. Colloidal confinement of polyphosphate on gold nanoparticles robustly activates the contact pathway of blood coagulation. Bioconjug. Chem. 27, 102-109 (2016).
48. Back, J., Sanchez, J., Elgue, G., Ekdahl, K. N. & Nilsson, B. Activated human platelets induce factor XIIa-mediated contact activation. Biochem. Biophys. Res. Commun. 391, 11-17 (2010).
49. Johne, J. et al. Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma. Biol. Chem. 387, 173-178 (2006).
50. Walsh, P. N. & Griffin, J. H. Contributions of human platelets to the proteolytic activation of blood coagulation factors XII and XI. Blood 57, 106-118 (1981).
51. Alvarenga, P. H. et al. Novel family of insect salivary inhibitors blocks contact pathway activation by binding to polyphosphate, heparin, and dextran sulfate. Arterioscler. Thromb. Vasc. Biol. 33, 2759-2770 (2013).
52. Jain, S. et al. Nucleic acid scavengers inhibit thrombosis without increasing bleeding. Proc. Natl Acad. Sci. USA 109, 12938-12943 (2012).
53. Smith, S. A. et al. Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. Blood 120, 5103-5110 (2012).
54. Malik, N. et al. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J. Control Release 65, 133-148 (2000).
55. Roberts, J. C., Bhalgat, M. K. & Zera, R. T. Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. J. Biomed. Mater. Res. 30, 53-65 (1996).
56. Travers, R. J., Shenoi, R. A., Kalathottukaren, M. T., Kizhakkedathu, J. N. & Morrissey, J. H. Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis. Blood 22, 3183-3190 (2014).
57. Parry, G. C., Erlich, J. H., Carmeliet, P., Luther, T. & Mackman, N. Low levels of tissue factor are compatible with development and hemostasis in mice. J. Clin. Invest. 101, 560-569 (1998).
58. Ni Ainle, F. et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood 114, 1658-1665 (2009).
59. Labberton, L., Kenne, E. & Renne, T. New agents for thromboprotection. A role for factor XII and XIIa inhibition. Hamostaseologie 35, 338-350 (2015).
60. Jaffer, I. H., Fredenburgh, J. C., Hirsh, J. & Weitz, J. I. Medical device-induced thrombosis: what causes it and how can we prevent it? J. Thromb. Haemost. 13(Suppl 1): S72-S81 (2015).
61. Svensson, M., Friberger, P., Lundstrom, O. & Stegmayr, B. Activation of FXII during haemodialysis. Scand. J. Clin. Lab. Invest. 56, 649-652 (1996).
62. Ponitz, V. et al. Activated factor XII type A predicts long-term mortality in patients admitted with chest pain. J. Thromb. Haemost. 7, 277-287 (2009).
63. Yau, J. W. et al. Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo. Acta Biomater. 8, 4092-4100 (2012).
64. Palekar, R. U., Vemuri, C., Marsh, J. N., Arif, B. & Wickline, S. A. Antithrombin nanoparticles inhibit stent thrombosis in ex vivo static and flow models. J. Vasc. Surg. http://dx.doi.org/10.1016/jjvs.2015.08.086 (2015).
65. Semeraro, F. et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement ofplatelet TLR2 and TLR4. Blood 118, 1952-1961 (2011).
66. Tans, G., Janssen-Claessen, T., Rosing, J. & Griffin, J. H. Studies on the effect of serine protease inhibitors on activated contact factors. Application in amidolytic assays for factor XIIa, plasma kallikrein and factor XIa. Eur. J. Biochem. 164, 637-642 (1987).
67. Renne, T., Gailani, D., Meijers, J. C. & Muller-Esterl, W. Characterization of the H-kininogen-binding site on factor XI: a comparison of factor XI and plasma prekallikrein. J. Biol. Chem. 277, 4892-4899 (2002).
68. Sala-Cunill, A. et al. Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions. J. Allergy Clin. Immunol. 135, 1031-1043 (2015).
69. He, S. et al. Fibrinogen depletion after plasma-dilution: impairment of proteolytic resistance and reversal via clotting factor concentrates. Thromb. Haemost. 111, 417-428 (2014).
70. Bjorkqvist, J. et al. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J. Clin. Invest. 125, 3132-3146 (2015).