Influence of gamma' fibrinogen splice variant on fibrin physical properties and fibrinolysis rate

Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):382-6. doi: 10.1161/01.ATV.0000109748.77727.3e. Epub 2003 Dec 1.

Abstract

Objective: A splice variant of fibrinogen, gamma', has an altered C-terminal sequence in its gamma chain. This gammaA/gamma' fibrin is more resistant to lysis than gammaA/gammaA fibrin. Whether the physical properties of gamma' and gammaA 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 gammaA and gamma' fibrinogens (1 mg/mL). gamma'/gamma' fibrin displayed a non-significant decrease in the density of fibrin fibers and slightly thicker fibers than gammaA/gammaA fibrin (12+/-2 fiber/10(-3) nm3 versus 16+/-2 fiber/10(-3) nm3 and 274+/-38 nm versus 257+/-41 nm for gamma'/gamma' and gammaA/gammaA 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, gamma' fibrin was found to be 3-times stiffer than gammaA fibrin (72.6+/-2.6 dyne/cm2 versus 25.1+/-2.3 dyne/cm2; 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 gammaA/gamma' fibrinogen in the clot is related primarily to an increase of fibrin cross-linking with only slight modifications of the clot architecture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics
  • Alternative Splicing / physiology*
  • Fibrin / chemistry*
  • Fibrin / metabolism
  • Fibrin / ultrastructure
  • Fibrinogen / chemistry*
  • Fibrinogen / metabolism
  • Fibrinogen / ultrastructure
  • Fibrinolysis / genetics
  • Fibrinolysis / physiology*
  • Humans
  • Microscopy, Electron, Scanning
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Structure-Activity Relationship

Substances

  • Protein Isoforms
  • Fibrin
  • Fibrinogen