title: Pharmacological modulation of fibrinolytic response - In vivo and in vitro studies.
abstract: 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.
authors: Department of Biopharmacy, Medical University of Białystok, Białystok, Poland. Electronic address: kkramk@wp.pl.
authors: Karol
authors: K
authors: Kramkowski
authors: Department of Pharmacodynamics, Medical University of Białystok, Białystok, Poland.
authors: Agnieszka
authors: A
authors: Leszczynska
authors: Department of Pharmacodynamics, Medical University of Białystok, Białystok, Poland; Higher Vocational School, Suwałki, Poland.
authors: Wlodzimierz
authors: W
authors: Buczko
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010958:Plasminogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D005343:Fibrinolytic Agents; D010958:Plasminogen; D010959:Tissue Plasminogen Activator
keywords: Drugs; Endothelium; Fibrynolysis; Platelets; Thrombosis