Influence of Fibrinogen Splice Variant on Fibrin Physical Properties and Fibrinolysis Rate
نویسندگان
چکیده
Objective—A splice variant of fibrinogen, , has an altered C-terminal sequence in its gamma chain. This A/ fibrin is more resistant to lysis than A/ A fibrin. Whether the physical properties of and A fibrin may account for the difference in their fibrinolysis rate remains to be established. Methods and Results—Mechanical and morphological properties of cross-linked purified fibrin, including permeability (Ks, in cm) and clot stiffness (G , in dyne/cm), were measured after clotting A and fibrinogens (1 mg/mL). / fibrin displayed a non-significant decrease in the density of fibrin fibers and slightly thicker fibers than A/ A fibrin (12 2 fiber/10 nm versus 16 2 fiber/10 nm and 274 38 nm versus 257 41 nm for / and A/ A fibrin, respectively; P NS). This resulted in a 20% increase of the permeability constant (6.9 1.7 10 9 cm versus 5.5 1.9 10 9 cm, respectively; P NS). Unexpectedly, fibrin was found to be 3-times stiffer than A fibrin (72.6 2.6 dyne/cm versus 25.1 2.3 dyne/cm; P 0.001). Finally, there was a 10-fold decrease of the fibrin fiber lysis rate. Conclusions—Fibrinolysis resistance that arises from the presence of A/ fibrinogen in the clot is related primarily to an increase of fibrin cross-linking with only slight modifications of the clot architecture. (Arterioscler Thromb Vasc Biol. 2004;24:382-386.)
منابع مشابه
Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis.
OBJECTIVE Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. METHODS AND RESULTS Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-p...
متن کاملThe αC domains of fibrinogen affect the structure of the fibrin clot, its physical properties, and its susceptibility to fibrinolysis
متن کامل
Fibrinogen and factor XIII at the intersection of coagulation, fibrinolysis and inflammation.
Fibrinogen and factor XIII are two essential proteins that are involved directly in fibrin gel formation as the final step of a sequence of reactions triggered by a procoagulant stimulus. Haemostasis is the most obvious function of the resulting fibrin clot. Different variables affect the conversion of fibrinogen to fibrin as well as the mode of fibrin polymerisation and fibrin crosslinking, he...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Fibrinogen gamma-chain splice variant alters fibrin formation and structure
Fibrinogen A/ results from alternative splicing of mRNA. This variant, which constitutes approximately 8% to 15% of plasma fibrinogen, contains FXIII and thrombin binding sites. Our objective was to investigate whether A/ differs in fibrin formation and structure from the more common variant A/ A. Both variants were separated and purified by anionexchange chromatography. Fibrin formation and cl...
متن کاملFibrinolysis in vivo Predicts a Favorable Outcome in Patients with Small Vessel Thrombi: Observations in Patients with Glomerular Thrombi during Treatment with Ancrod
= Abstract =Fibrin deposits injure small vessels. To evaluate the effect of fibrinolysis, patients with glomerular diseases having glomerular thrombi received the snake venom enzyme, ancrod, for 14 days. Within 48 hours, the mean level of fibrin/fibrinogen degradation products(FOP) was very high, and bimodally distributed, defining lowln = 11) and high(n = 18) FOP responses. In the low FOP grou...
متن کامل