title: Alterations of fibrin network structure mediated by dermatan sulfate.
abstract: Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II (HCII) to enhance thrombin inhibition. It has also been reported that DS has a profibrinolytic effect. We have evaluated the effects of DS solutions (4-20 μg/mL) on the formation (by kinetic studies), structure (by electron microscopy and compaction assays) and lysis (with urokinase-type plasminogen activator) of plasma fibrin networks. The results showed that DS significantly prolonged the lag phase and decreased the fibrin formation rate and the optical density of the final networks versus control, in a concentration dependent way. DS-associated networks presented a minor network percentage compared with control, composed of lower number of fibers per field, which resulted significantly thinner and longer. Moreover, DS rendered gels more sensible to rupture by centrifugal force and more susceptible to lysis. When fibrin formation kinetic assays were performed with purified fibrinogen instead of plasma, in the absence of HCII, the optical density of final DS-associated networks was statistically lower than control. Therefore, a direct effect of DS on the thickness of fibers was observed. Since in all in vitro assays low DS concentrations were used, it could be postulated that the fibrin features described above are plausible to be found in in vivo thrombi and therefore, DS would contribute to the formation of less thrombogenic clots.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, piso 4°, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. amlauri@qb.fcen.uba.ar
authors.forename: Ana María
authors.initials: AM
authors.lastname: Lauricella
authors.forename: María Mercedes
authors.initials: MM
authors.lastname: Castañon
authors.forename: Lucía C
authors.initials: LC
authors.lastname: Kordich
authors.forename: Irene L
authors.initials: IL
authors.lastname: Quintana
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism* / Q000502:physiology; D002417:Cattle; D003871:Dermatan Sulfate / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*; D011485:Protein Binding / Q000502:physiology
chemical_list: D000925:Anticoagulants; D003871:Dermatan Sulfate; D005337:Fibrin