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Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection

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Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection. / Labberton, Linda ; Kenne, Ellinor; Long, Andy T; Nickel, Katrin F; Di Gennaro, Antonio; Rigg, Rachel A; Hernandez, James S; Butler, Lynn; Maas, Coen; Stavrou, Evi X; Renné, Thomas.

In: NAT COMMUN, Vol. 7, 06.09.2016, p. 12616.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Labberton, L, Kenne, E, Long, AT, Nickel, KF, Di Gennaro, A, Rigg, RA, Hernandez, JS, Butler, L, Maas, C, Stavrou, EX & Renné, T 2016, 'Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection', NAT COMMUN, vol. 7, pp. 12616. https://doi.org/10.1038/ncomms12616

APA

Labberton, L., Kenne, E., Long, A. T., Nickel, K. F., Di Gennaro, A., Rigg, R. A., Hernandez, J. S., Butler, L., Maas, C., Stavrou, E. X., & Renné, T. (2016). Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection. NAT COMMUN, 7, 12616. https://doi.org/10.1038/ncomms12616

Vancouver

Labberton L, Kenne E, Long AT, Nickel KF, Di Gennaro A, Rigg RA et al. Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection. NAT COMMUN. 2016 Sep 6;7:12616. https://doi.org/10.1038/ncomms12616

Bibtex

@article{894d9ab9de234454bf7a8f2cfabbd4d8,
title = "Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection",
abstract = "Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.",
keywords = "Journal Article, POM-Newsletter",
author = "Linda Labberton and Ellinor Kenne and Long, {Andy T} and Nickel, {Katrin F} and {Di Gennaro}, Antonio and Rigg, {Rachel A} and Hernandez, {James S} and Lynn Butler and Coen Maas and Stavrou, {Evi X} and Thomas Renn{\'e}",
note = "Paper of the Month September, bitte die Erstautorin (Doktorandin), Frau Labberton dem Institut zuschreiben. Danke sehr!",
year = "2016",
month = sep,
day = "6",
doi = "10.1038/ncomms12616",
language = "English",
volume = "7",
pages = "12616",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection

AU - Labberton, Linda

AU - Kenne, Ellinor

AU - Long, Andy T

AU - Nickel, Katrin F

AU - Di Gennaro, Antonio

AU - Rigg, Rachel A

AU - Hernandez, James S

AU - Butler, Lynn

AU - Maas, Coen

AU - Stavrou, Evi X

AU - Renné, Thomas

N1 - Paper of the Month September, bitte die Erstautorin (Doktorandin), Frau Labberton dem Institut zuschreiben. Danke sehr!

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.

AB - Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.

KW - Journal Article

KW - POM-Newsletter

U2 - 10.1038/ncomms12616

DO - 10.1038/ncomms12616

M3 - SCORING: Journal article

C2 - 27596064

VL - 7

SP - 12616

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -