Thrombin-mediated fibrinogen conversion to fibrin and fibrin monomer cross-linking by activated factor (F)XIII result in the formation of a clot, which is relatively resistant to mechanical and enzymatic degradation. Clot structure, characterized by clot porosity and fiber thickness, plays a role in atherothrombotic vascular disease. In patients with advanced coronary artery disease, reduced fibrin clot permeability was first documented in 1992. Dense clot fiber networks have been found in survivors of myocardial infarction aged < 50 years and in their first-degree relatives. Altered fibrin clot architecture has also been reported in dyslipidemia and in diabetes. There is evidence that a number of genetic and environmental factors affect fibrin clot architecture and clot resistance to lysis. Elevated inflammatory markers have been associated with decreased clot permeability and lower clot susceptibility to fibrinolysis. A similar effect exerts hiperhomocysteinemia. Favorable changes in fibrin clot structure can be induced by drug administration. Acetylsalicylic acid (aspirin) at therapeutic doses has been reported to increase clot permeability and enhance clot lysability. Recently, we have shown that lipid-lowering agents (statins, fibrates) and angiotensin-converting enzyme inhibitors alter fibrin clot structure similarly to aspirin. The most probable mechanisms underlying altered clot architecture in patients at risk of cardiovascular disease are a decrease/increase in fibrinogen or thrombin levels, or nonenzymatic modification of the fibrinogen molecules such as oxidation or glycation. Despite substantial experimental evidence, it remains to be determined to what extent fibrin clot properties influence the prevention and treatment of cardiovascular disease.
Keywords: Fibrin, clot, cardiovascular disease, risk factor, thrombosis, genetic polymorphism
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