Fibrinogen γ′ increases the sensitivity to activated protein C in normal and factor V Leiden plasma

Omarova, Farida; Willige, Shirley Uitte de; Simioni, Paolo; Ariëns, Robert A. S.; Bertina, Rogier M.; Rosing, Jan; Castoldi, Elisabetta

doi:10.1182/blood-2014-02-554055

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…On the contrary, epidemiologic data suggest that decreased levels of fibrinogen γ′ may be associated with venous thrombosis. 87 The antithrombotic role of fibrinogen γ′ may be due to the aforementioned capacity of fibrinogen γ′ to counteract the plasma APC resistance, the most common risk factor for venous thrombosis, 40,42 and this hypothesis has been supported by several observations in animal models. 39,88,89 Studies in baboons showed that a γ′ 410 to 427 peptide inhibited fibrin-rich thrombus formation and, to a lesser extent, platelet-rich thrombus formation.…”

Section: Venous Thrombosismentioning

confidence: 93%

“…41 Omarova et al later showed that fibrinogen γ′ increases plasma activated Protein C (APC) sensitivity. 42 They observed increased APC resistance in carriers of (FGG) haplotype 2, which was associated with reduced γ′ levels. γA/γ′ resulted in an increased sensitivity of plasma to the anticoagulant action of APC in thrombin generation-based assays.…”

Section: Interactions With Fv Fviii the Protein C System And Histimentioning

confidence: 97%

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The (Patho)physiology of Fibrinogen γ′

Macrae

Domingues

Casini

et al. 2016

Semin Thromb Hemost

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Fibrinogen γ' is a splice variant of the fibrinogen γ-chain, which leads to a negatively charged extension at the C-terminus of the γ-chain. In fibrinogen, the splice variant appears mainly as a heterodimer with the common γA chain, as γA/γ' fibrinogen. This variant has been shown to modulate thrombin and factor XIII (FXIII) activity, influence clot architecture, and lack a platelet-binding site. Clinically γA/γ' fibrinogen levels have been associated with arterial and venous thromboses, indicating that the functional effects of γA/γ' fibrinogen may contribute to the pathology of thrombosis. In view of the fact that the splice variant has several functional effects and is found so far in all individuals, this review provides an up-to-date summary of the key biologic aspects of this fibrinogen variant and discusses any inconsistencies in current reports.

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Section: Venous Thrombosismentioning

confidence: 93%

Section: Interactions With Fv Fviii the Protein C System And Histimentioning

confidence: 97%

The (Patho)physiology of Fibrinogen γ′

Macrae

Domingues

Casini

et al. 2016

Semin Thromb Hemost

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show abstract

“…Moreover, Omarova et al showed that fibrinogen ' increases the sensitivity of plasma to the inhibition of clotting to activated protein C [23]. So while ' on one hand protects thrombin against degradation and increases thrombin generation in plasma, it inhibits exosite II driven procoagulant reactions on the other hand.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Duval

Ariëns

2017

Matrix Biology

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ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ÔØ Å ÒÙ× Ö ÔØ A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractFibrin is an important matrix protein that provides the backbone to the blood clot, promoting tissue repair and wound healing. Its precursor fibrinogen is one of the most heterogenous proteins, with an estimated 1 million different forms due to alterations in glycosylation, oxidation, single nucleotide polymorphisms, splice variation and other variations. Furthermore, ligation by transglutamimase factor XIII (cross-linking) adds to the complexity of the fibrin network. The structure and function of the fibrin network is in part determined by this natural variation in the fibrinogen molecule, with major effects from slice variation and cross-linking. This mini-review will discuss the direct effects of fibrinogen EC and fibrinogen ' splice variation on clot structure and function and also discuss the additional role of fibrinogen ' as thrombomodulin II. Furthermore, the effects of crosslinking on clot function will be described. Splice variation and cross-linking are major determinants of the structure and function of fibrin and may therefore impact on diseases affecting bleeding, thrombosis and tissue repair.

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“…However, evidence has emerged to support that FGG 10034C N T variant (rs2066865), located in the 3′-end non-coding sequence of FGG-haplotype-2 (FGG-H2), is associated with an increased risk of venous thrombosis [13]. It is possible that the lack of fibrinogen (particularly fibrinogen γ′) in FGG-H2 reduces the plasma APC sensitivity and enhances APC resistance [14]. The existence and prevalence of this variation and its association with Chinese DVT patients should be investigated in further studies.…”

Section: Discussionmentioning

confidence: 99%

Association between genetic polymorphisms and deep vein thrombosis in a Chinese population

Jia

Jiao

Ding

et al. 2015

Thrombosis Research

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Fibrinogen γ′ increases the sensitivity to activated protein C in normal and factor V Leiden plasma

Abstract: Key Points Fibrinogen, and particularly fibrinogen γ′, counteracts plasma APC resistance, the most common risk factor for venous thrombosis. The C-terminal peptide of the fibrinogen γ′ chain inhibits protein C activation, but still improves the response of plasma to APC.

Cited by 17 publications

References 34 publications

The (Patho)physiology of Fibrinogen γ′

The (Patho)physiology of Fibrinogen γ′

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Association between genetic polymorphisms and deep vein thrombosis in a Chinese population

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