Role of coagulation factor XIII in cardio- and cerebrovascular diseases

Abstract

In the final step of the clotting cascade coagulation factor XIII (FXIII) is activated by thrombin. The activated enzyme (FXIIIa) has an important role in the final stage of blood coagulation in cross-linking soluble fibrin to a stable insoluble clot. The role of FXIII in cardio- and cerebrovascular diseases has been investigated recently. The widespread Val34Leu polymorphism in the gene coding for the FXIII subunit A (FXIII Val34Leu) has been shown to protect against myocardial infarction and ischemic stroke, but is also associated with an increased risk for hemorrhagic stroke. Additionally, FXIII Val34Leu is supposed to be protective against pulmonary embolism and deep vein thrombosis. As possible mechanisms for the antithrombotic effect, premature depletion of the mutant protein from circulation and altered fibrin structures of clots cross-linked by the mutant FXIIIa are under discussion. The connection between FXIII and the insulin resistance syndrome also attracts attention, i.e. the interaction between a component of the coagulation cascade and thus a thrombotic risk factor and classical atheromatous risk factors. Therefore, FXIII must be considered as another coagulation factor contributing to complex interactions between genes and environment important for the pathogenesis of cardio- and cerebrovascular and thromboembolic diseases.