title: [The role of post-translational modification of fibrinogen in the pathogenesis of thrombosis].
abstract: 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.
authors.affiliation: University of Lodz, Poland, Department of General Biochemistry.
authors.forename: Justyna
authors.initials: J
authors.lastname: Tadeusiewicz
authors.affiliation: University of Lodz, Poland, Department of General Biochemistry.
authors.forename: Paweł
authors.initials: P
authors.lastname: Nowak
mesh_terms: D005110:Extracellular Space / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D054879:Halogenation; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D006710:Homocysteine; D005337:Fibrin; D005340:Fibrinogen; D008239:Lysine
keywords: chlorination; fibrinogen; glycation; homocysteinylation; nitration