Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics

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.

Transcriptome-based screening of intracellular pathways and angiogenesis related genes at different stages of thiram induced tibial lesions in broiler chickens

“…Whereas on day 6, it was not differentially expressed. Sixthly, F13A1 is a key molecule, which coagulates the blood and, played role in angiogenesis and tissue repairing when interacts with vascular endothelial growth factor receptor 2 (VEGFR2) and integrin αVβ3 for optimal tissue healing [25]. Seventhly, CCSAP is the only gene which differentially expressed and upregulated on both 2 and 15 days.…”

Inflammation and Cardiovascular Cross Talk in Ischemic Vascular Diseases

“…Recruited inflammatory cells can remove debris and facilitate the repair process; conversely, unrestrained inflammation inhibits optimal healing leading to adverse events. Moreover, other mediators such as some key coagulation factors might influence innate immunity as well as cell-mediated reactions like healing, response to tissue injury, or inflammatory processes [4, 5]. Overall, as recently suggested, the different immune/inflammatory cell subsets act as messengers implicated in novel inflammatory networks that link different organ systems enlarging the continuum beyond the myocardium and blood vessels in a more integrative pathophysiology standpoint [6].…”

Association of factor XIII Val34Leu polymorphism and coronary artery disease: A meta-analysis

“…Factor XIII influences wound healing in several tissues, including cardiomyocytes, by exerting multiple plasma and cellular functions. Moreover, the proangiogenic function of factor XIII is directed by the interaction of vascular endothelial growth factor receptor 2 and integrin aVb 3 on the cell membrane [51]. Certain studies showed that low factor XIIIA level correlated with a poor prognosis with regard to MI [52,53].…”