Fibrinogen is a precursor of
fibrin, which is the main component of the
blood clot. The opposite of coagulation is fibrinolysis. The proper functioning of both systems allow to maintain a hemostasis. Increasing level of
fibrinogen is an important risk factor for
myocardial infarction or
ischemic stroke. Reactive
oxygen,
nitrogen and
chlorine species are created in inflammatory conditions,
ischemia and tissues reperfusion. They can modify the
fibrinogen molecule. The most important changes are associated with nitration and chlorination of
tyrosine residues, oxidation of
methionine,
histidine and
tryptophan residues, as well as formation
dityrosine and carbonyl groups. Moreover, structure of
fibrinogen is modified by glycation and homocysteinylation in
hyperglycemia and
hyperhomocysteinemia conditions. Non-enzymatic posttranslational modifications of
fibrinogen contribute to formation of thrombogenic
fibrin structure. The degree of
fibrinogen modification is responsible for fiber structure, packing and susceptibility of
fibrin clots to fibrinolysis. Additionally, the viscoelastic properties are changed. Resistance to fibrinolysis is largely associated with the modification of
lysine residues in the
protein molecule. Each of these alternations may contribute to increased risk of arterial and
venous thrombosis.