Pharmacological modulation of fibrinolytic response - In vivo and in vitro studies

Fibrinolysis is an action of converting plasminogen by its activators, like tissue- or urokinase-type plasminogen activators (t-PA, u-PA), to plasmin, which in turn cleaves fibrin, thereby causing clot dissolution and restoration of blood flow. Endothelial cells release t-PA, prostacyclin (PGI2) and nitric oxide (NO), the potent factors playing a crucial role in regulation of the fibrinolytic system. Since blood platelets can release not only prothrombotic, but also antifibrinolytic factors, like plasminogen activator inhibitor type-1 (PAI-1), they are involved in fibrynolysis regulation. Therefore agents enhancing fibrinolysis can be preferred pharmacologicals in many cardiovascular diseases. This review describes mechanisms by which major cardiovascular drugs (renin-angiotensin-aldosterone system inhibitors, statins, adrenergic receptors and calcium channel blockers, aspirin and 1-methylnicotinamide) influence fibrinolysis. The presented data indicate, that the influence of these drugs on endothelium-blood platelets interactions via NO/PGI2 pathway is fundamental for its antithrombotic and profibrinolytic action. We also described new approaches for intravital confocal real-time imaging as a tool useful to investigate mechanisms of thrombus formation and the effects of drugs affecting haemostasis and mechanisms of their action in the circulation.