Influence of γ′ Fibrinogen Splice Variant on Fibrin Physical Properties and Fibrinolysis Rate

J. P. Collet, C. Nagaswami, D. H. Farrell, G. Montalescot, J. W. Weisel

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Abstract

Objective-A splice variant of fibrinogen, γ′, has an altered C-terminal sequence in its gamma chain. This γA/γ′ fibrin is more resistant to lysis than γA/γA fibrin. Whether the physical properties of γ′ and γA 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 cm2) and clot stiffness (G′, in dyne/cm2), were measured after clotting γA and γ′ fibrinogens (1 mg/mL). γ′/γ′ fibrin displayed a non-significant decrease in the density of fibrin fibers and slightly thicker fibers than γA/γA fibrin (12±2 fiber/10 -3nm3 versus 16±2 fiber/10-3nm 3 and 274±38 nm versus 257±41 nm for γ′/γ′ and γA/γA fibrin, respectively; P = NS). This resulted in a 20% increase of the permeability constant (6.9±1.7 10-9 cm2 versus 5.5 ± 1.9 10 -9 cm2, respectively; P = NS). Unexpectedly, γ′ fibrin was found to be 3-times stiffer than γA fibrin (72.6±2.6 dyne/cm2 versus 25.1±2.3 dyne/cm 2; 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 γA/γ′ fibrinogen in the clot is related primarily to an increase of fibrin cross-linking with only slight modifications of the clot architecture.

Original languageEnglish (US)
Pages (from-to)382-386
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2004

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Keywords

  • Coagulation
  • Fibrin
  • Fibrinogen
  • Fibrinolysis
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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