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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5403035
- author
- Dickneite, Gerhard
; Herwald, Heiko
LU
; Korte, Wolfgang
; Allanore, Yannick
; Denton, Christopher P.
and Cerinic, Marco Matucci
- organization
- publishing date
- 2015
- 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
- Schattauer GmbH
- external identifiers
-
- wos:000352464000003
- scopus:84928026945
- pmid:25652913
- 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
- 2016-04-01 15:02:25
- date last changed
- 2022-04-06 21:52:10
@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}},
keywords = {{Coagulation; factor XIII; infection; scleroderma; wound healing}},
language = {{eng}},
number = {{4}},
pages = {{686--697}},
publisher = {{Schattauer GmbH}},
series = {{Thrombosis and Haemostasis}},
title = {{Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions}},
url = {{https://lup.lub.lu.se/search/files/4309367/8312546.pdf}},
doi = {{10.1160/TH14-07-0625}},
volume = {{113}},
year = {{2015}},
}