The role of factor XIIIVal34Leu in cardiovascular disease.

Blood coagulation factor XIII (also called fibrinplasma as a tetramer (A 2 B 2 ).12 All A-subunit molecules in plasma are in complex with the B-subunit (carrier stabilizing factor1) plays an important role in clot stabilization by crosslinking fibrin chains.2 Factor XIII protein) at a concentration of approximately 21 mg/ml, whereas the B-subunit is present in both free and (FXIII) was discovered over 70 years ago by Barkan et al., who observed the insolubility of fibrin clots complexed form.13 The total B concentration is around 21 mg/ml, about half of which circulates free in plasma in the presence of calcium.3 Most studies on FXIII have been carried out in patients with FXIII deficiency (10 mg/ml).14 In circulation, more than 90% of FXIII is bound to fibrinogen by a binding site on fibrinogen which results in a serious bleeding diathesis, defective wound healing and a high risk of miscarriage in for the B-subunit. Through this interaction, fibrinogen serves as a carrier for the plasma zymogen.15 the deficient female.4,5 Most of these subjects show no plasma FXIII activity because of a complete Activation of FXIII results in FXIIIA∞ through release of an activation peptide consisting of 37 amino acids.16 absence of the A-subunit in plasma, platelets and monocytes.6 Little is known about the role of FXIII Dissociation of the A∞ 2 B 2 tetramer is promoted in the presence of calcium. Both steps (release of activation in vascular diseases. Although Kloczko et al. showed increased levels of FXIII A-subunit antigen in patients peptide and dissociation of the subunits) are essential for the complete activation of the FXIII zymogen.17 with obliterative atherosclerosis of the lower limbs and in patients with diabetic angiopathy, small The dissociation of the tetramer is also enhanced in the presence of fibrinogen, and the release of the patient numbers make the interpretation of these data difficult.7,8 However, increased plasma concenactivation peptide from the A-subunit is promoted by the proteolytic products of fibrinogen (polymerized tration of cross-linked fibrin polymers in acute myocardial infarction has been described, assuming des-A, des-A,B fibrinogen).18–20 This promoting effect on the release of the activation peptide is lost when the presence of increased plasma FXIII plasma activity in patients with coronary artery disease.9 Results FXIII-catalysed cross-linked fibrin starts to form.21 Activated factor XIII catalyses the covalent crosslinking from our laboratory add further support in the involvement of FXIII in cardiovascular diseases.10,11 of the c and a chains of fibrin, increasing the mechanical strength of fibrin, and cross-linking of Here we discuss some new insights regarding the role of FXIII in vascular disease, with emphasis on antiplasmin increases its resistance to fibrinolysis.22 Additionally, a number of proteins are substrates for a common polymorphism in the A-subunit gene of FXIII (FXIIIVal34Leu) and its association with factor XIII, such as a 2 -antiplasmin, von Willebrand factor, factor FVII, collagen, fibronectin, thrombosponmyocardial infarction, stroke and venous thromboembolism. din and vitronectin.23–26