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Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions

Dickneite, Gerhard; Herwald, Heiko LU ; Korte, Wolfgang; Allanore, Yannick; Denton, Christopher P. and Cerinic, Marco Matucci (2015) In Thrombosis and Haemostasis 113(4). p.686-697
Abstract
Coagulation Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of alpha(2)-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and alpha(v)beta(3) integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and... (More)
Coagulation Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of alpha(2)-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and alpha(v)beta(3) integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to. fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces-cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dys-regulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Coagulation, factor XIII, infection, scleroderma, wound healing
in
Thrombosis and Haemostasis
volume
113
issue
4
pages
686 - 697
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000352464000003
  • scopus:84928026945
ISSN
0340-6245
DOI
10.1160/TH14-07-0625
language
English
LU publication?
yes
id
afb81447-b429-4ee8-a9be-40edc7a894ab (old id 5403035)
date added to LUP
2015-06-01 09:22:22
date last changed
2017-09-10 04:22:01
@article{afb81447-b429-4ee8-a9be-40edc7a894ab,
  abstract     = {Coagulation Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of alpha(2)-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and alpha(v)beta(3) integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to. fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces-cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dys-regulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.},
  author       = {Dickneite, Gerhard and Herwald, Heiko and Korte, Wolfgang and Allanore, Yannick and Denton, Christopher P. and Cerinic, Marco Matucci},
  issn         = {0340-6245},
  keyword      = {Coagulation,factor XIII,infection,scleroderma,wound healing},
  language     = {eng},
  number       = {4},
  pages        = {686--697},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions},
  url          = {http://dx.doi.org/10.1160/TH14-07-0625},
  volume       = {113},
  year         = {2015},
}