A n altered fibrin network architecture has been associated with premature coronary artery disease (CAD). 1,2 Hypofibrinolysis, ie, impaired dissolution of fibrin in blood clots, is another common finding in such patients. Hypofibrinolysis is associated with elevated activity of inhibitors of the fibrinolytic process, particularly of plasminogen activator inhibitor-1 (PAI-1) 3 and thrombin activatable fibrinolysis inhibitor (TAFI), 4 but it is also influenced by the characteristics of the fibrin network itself. 5,6 However, previous studies on fibrin architecture, its regulation, and implications for CAD have been hampered by imperfect and/or incomplete methodology. Thus, the relationships between fibrin structure, fibrinolytic function, and premature CAD warrant further thorough examination. This issue of Arteriosclerosis, Thrombosis, and Vascular Biology features a comprehensive investigation of physical and viscoelastic characteristics of fibrin clots formed ex vivo from plasma samples, their relationships to fibrinolysis rate, and potential role in CAD. 7
See page 2567Both the morphology and mechanical properties of fibrin influence susceptibility to fibrinolysis. Fibrin structure is generally assessed by using liquid permeation, light scattering, scanning electron microscopy, and confocal microscopy, from which variables such as the fiber thickness, length and density, and the number of branch points and porosity of the network are derived. 8 Blunted fibrinolysis is associated with a tight fibrin structure composed of thin and short fibers with increased number of branch points, and small pores. 5,6 Individual thick fibers are actually lysed at a slower rate, 9 but tight network configurations display a significantly higher fiber density compared with loose structures, which renders them more difficult to be lysed because there are more fibers to be processed 6 and increased restriction to the permeation of fibrinolytic factors through the network.The mechanical properties of fibrin can be quantified by determining the response to forces to which fibers are subjected. 10 Either static or dynamic measurements can be made, oscillatory motion being an example of the latter. Recording of the oscillations of a torsion pendulum attached to a sample (clot) on careful application of shear forces allows calculations of the storage modulus, which reflects the stiffness or resistance of the clot to deformation. 11 In general, clots with increased stiffness are digested more slowly by plasmin than less stiff clots. This was clearly shown in experiments in which the stiffness of the clot and its resistance to fibrinolysis increased in parallel on addition of factor XIII, whereas inhibitors of the factor XIII-catalyzed reactions greatly reduced both clot stiffness and lytic resistance. 12 Also, fibrin formed with a recombinant fibrinogen truncated at A␣ chain residue 251 was less stiff and digested faster in plasmin-catalyzed experiments than control fibrin formed with recombinant fibrinogen with common A␣ chains contain...