Editorial [ Hot Topic: Structural Basis for Variable Lytic Susceptibility of Fibrin Bridging Structure with Function in Fibrinolysis (Guest Editor: K. Kolev) ]

Cardiovascular and cerebrovascular diseases continue to be a major public health burden worldwide. According to the WHO data the mortality related to atherothrombosis is the leading cause of death responsible for 22.3% of the total deaths in the world preceding infectious diseases (19.1%) and neoplasms (12.5%) [1]. Some of the improvements in death rates seen in many developed countries may be partly attributable to the application of thrombolytic therapy for myocardial infarction or ischemic stroke [2, 3], designed to lyse the clots blocking the arteries and restore blood flow as quickly as possible. This therapeutic approach is based on the administration of plasminogen activators (urokinase, streptokinase, tissue-type plasminogen activator and its recombinant variants), which convert the plasminogen in blood plasma, on the surface of or inside the thrombi to plasmin which then dissolves fibrin, the solid matrix of thrombi. However, persistent recanalization of the occluded blood vessels often fails (in 15 to 40% of patients) and efficient doses of current fibrinolytic agents have significant bleeding side-effects [4]. These limitations of fibrinolytic therapy maintain a continuous interest in the basic research of the molecular mechanisms underlying fibrin dissolution, which could help the development of more efficient and safe clot busting agents. The present collection of reviews explores recent advances in understanding the interconnections between the structure of the fibrin clots and the action of the enzymes destroying it. In their review entitled “The biochemical and physical process of fibrinolysis and effects of clot structure and stability on the lysis rate” Weisel and Litvinov (University of Pennsylvania, Philadelphia) present a comprehensive overview of all participants in the fibrinolytic process, which helps the reader to unify the more specialized aspects of the molecular mechanisms discussed in the accompanying papers [5]. A special focus of this review is the microscopic structure of the fibrin mesh and its impact on the enzymatic steps of the dissolution process. The minireview entitled “Searching for differences between fibrinogen and fibrin that affect the initiation of fibrinolysis” contributed by Doolittle (University of California, San Diego) summarizes the ultrastructural changes accompanying the conversion of fibrinogen to fibrin [6]. This minireview addresses the structural determinants of the self-destructing nature of fibrin as opposed to fibrinogen, which co-exists in peace with all participants in fibrinolysis. Muszbek, Bagoly, Bereczky and Katona (University of Debrecen Medical and Health Science Center, Debrecen) explain the basic biochemical function of factor XIII in their minireview entitled “The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis” [7]. The stability of fibrin conferred by factor XIIIa is discussed in the context of clinical states of thrombosis related to variations in factor XIII level and its genetic polymorphisms. In the minireview entitled “Alterations of fibrinogen structure in human disease” Hoffman (Duke University Medical Center, Durham) explores the consequences of post-translational modification of fibrinogen through oxidation, nitration, homocysteinylation and glycation [8]. This minireview helps the understanding of the altered fibrinolysis in disease states with increased rate of covalent modification of proteins (e.g. diabetes). Longstaff, Williams and Thelwell (National Institute for Biological Standards and Control, South Mimms) approach the structure-function relationships in fibrinolysis from the side of plasminogen activators in their minireview entitled “Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy” [9]. A special focus in this minireview is the methodology for evaluating and modeling fibrinolysis in vitro as a tool for assessing new thrombolytic agents. In the last review of the series, entitled “Role of cellular elements in thrombus formation and dissolution” Wohner (Semmelweis University, Budapest) presents a cellular view of fibrinolysis [10]. This minireview outlines the contribution of platelets, leukocytes and red blood cells to the modification of fibrin structure as well as their direct effects on discrete steps of fibrinolysis........