Title:Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics
Volume: 22
Issue: 11
Author(s): Donato Gemmati, Marco Vigliano, Francesco Burini, Rosella Mari, Hodeib Hossam Abd El Mohsein, Francesco Parmeggiani and Maria L. Serino
Affiliation:
Keywords:
Coagulation Factor XIII (FXIII), wound-healing, tissue repair, inflammation, pharmacogenetics, cardiovascular diseases,
degenerative disease, stem-cells.
Abstract: Factor XIII (FXIII) is a key molecule in the field of blood coagulation and in the last decades it has
weakened attention within the field of angiogenesis and tissue repair. FXIII positively influences wound healing in
several tissues by exerting multiple plasma and cellular functions. In the field of haemostasis, FXIII cross-links the
neo formed fibrin fibers and supports platelet adhesion to the damaged sub-endothelium warranting a solid architecture.
In addition, the pro-angiogenic functions of FXIII are directed by the interaction of vascular endothelial
growth factor receptor 2 (VEGFR2) and the integrin αVβ3, on the cell membrane, favouring an important step in the
formation of granulation tissue at the wound site for optimal tissue healing. Conversely, the same mechanisms
could lead to undesired increased neovascularisation, for example in inflammatory bowel disease or in the retinal
degenerative pathologies. The classical symptoms of FXIII deficiency span from intracranial haemorrhage to delay bleeding or the staying
of chronic wounds in the skin including impaired mucosal healing. In this view, FXIII bridges primary haemostasis, coagulation and
definite tissue healing. Another important recently discovered function ascribed to FXIII is its ability to limit bacterial spreading from the
lesion by incorporating specific macromolecules addressed to cellular infiltration, favouring in turn cell migration and survival, as observed
also in fibrin-heart cultures for stem cell recruitment. In the field of the novel prognostic biomarkers, the monitoring of the residual
circulating FXIII level during acute myocardial infarction has been considered predictive of the post-myocardial infarction healing.
Accordingly, adequate FXIII levels can drive and predict the prognosis of complex diseases and the outcome of the associated therapies
or interventions. In addition, peculiar pharmacogenetics aspects of the FXIII gene are of extraordinary interest. The present review accounts
for the recognized role of FXIII in the healing process and gives some examples on how to use it as prognostic biological/
molecular marker or as potential tailored therapeutic molecule in complex diseases.