title: Functional impact of oxidative posttranslational modifications on fibrinogen and fibrin clots.
abstract: Fibrinogen is a circulating multifunctional plasma protein vital for hemostasis. Activation of the coagulation cascade converts soluble fibrinogen to insoluble polymerized fibrin, which, along with platelets, forms the hemostatic clot. However, inappropriate formation of fibrin clots may result in arterial and venous thrombotic disorders that may progress to life-threatening adverse events. Often thrombotic disorders are associated with inflammation and the production of oxidants. Fibrinogen represents a potential target for oxidants, and several oxidative posttranslational modifications that influence fibrinogen structure and function have been associated with disease pathogenesis. Here, we review various oxidative modifications of fibrinogen and the consequences of these modifications on protein structure and the ability to form fibrin and how the resulting alterations affect fibrin architecture and viscoelastic and biochemical properties that may contribute to disease.
authors.affiliation: Department of Pediatrics and Department of Pharmacology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Department of Cell and Developmental Biology, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
authors.affiliation: Department of Pediatrics and Department of Pharmacology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ischirop@mail.med.upenn.edu.
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011499:Protein Processing, Post-Translational
chemical_list: D005337:Fibrin; D005340:Fibrinogen
keywords: Coagulation; Fibrin; Fibrinogen; FpA/FpB; Free radicals; GSH; GSNO; MPO; Nitrotyrosine; Oxidation; PPP; PTM; S-nitrosoglutathione; Thrombosis; VTE; fibrinopeptide A/B; glutathione; myeloperoxidase; platelet-poor plasma; posttranslational modification; tPA; tissue plasminogen activator; venous thromboembolism