Objective-Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results-Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (PϽ0.05). Fibrin of young CAD patients was stiffer (Pϭ0.002), made of numerous (Pϭ0.002) and shorter fibers (Pϭ0.04), and lysed at a slower rate than that of controls (Pϭ0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions-This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. Key Words: acute coronary syndromes Ⅲ coagulation Ⅲ fibrinolysis Ⅲ pathophysiology Ⅲ fibrinogen Ⅲ thrombophilia T he mechanical properties of clots and their major constituent fibrin are normally finely tuned to optimize bleeding control while also minimizing their effect on atherothrombosis. 1,2 A decreased rate of fibrinolysis and increased thrombosis are generally associated with stiff clots, although such relationships are complex. 3,4 Many factors that affect clot structure have a great impact on the mechanical properties fibrin and fibrinolysis through modifications of various steps in the fibrin polymerization process and clot stabilization. 1,4,5 See page 2419Premature coronary artery disease (CAD) is associated with increased plasma levels of prothrombotic and proinflammatory biomarkers, including fibrinogen and plasminogen activator inhibitor (PAI) type 1, which are known to favor hypofibrinolysis 6 and to be independent predictors of CAD. 7,8 Epidemiological studies have also revealed a relationship between myocardial infarction (MI) and reduced permeability and increased stiffness of fibrin, especially in young post-MI patients. 9 These aspects of altered fibrin clot network architecture were not found to be attributable to classic risk factors including fibrinogen concentrations or common polymorphisms. 2 However, the relationships among premature CAD, abnormal fibrin physical properties, and hypofibrinolysis remain little explored. The lack of appropriately designed studies of the physical properties of fibrin, including simultaneous determination of viscoelastic and morphological properties o...

"Degenerative" aortic valve stenosis appears to be a chronic inflammatory process associated with atherosclerotic risk factors. The coexistence of neoangiogenesis, T-lymphocyte infiltration, adhesion molecules, and hsp60 gene expression indicates an active immunomediated process in the final phases of the disease.

Nitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties.

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