[Endothelium and endogenous fibrinolysis].
Reduced activity of the endogenous fibrinolytic system contributes to intramural deposition of microthrombi in atherogenesis and to intraluminal deposition of thrombi leading to acute complications of atherosclerosis such as acute coronary syndromes. Endogenous fibrinolytic activity is predominantly regulated by the plasminogen activator inhibitor type 1 (PAI-1). Increased activity of PAI-1 leading to reduced endogenous fibrinolytic activity has been identified as an important independent risk factor for cardiovascular disease. Vascular endothelial cells form a barrier between the circulating blood with its dynamic balance between ongoing thrombosis and fibrinolysis and the subendothelial layers of the vascular wall with their prothrombotic activity. In addition, endothelial cells synthesize and secrete substantial amounts of plasminogen activators and their inhibitor PAI-1. Thus, endothelium plays an important role in the regulation of endogenous fibrinolysis. After describing the components of the endogenous fibrinolytic system and its interactions, this review focuses on the impact on endogenous fibrinolysis by the renin angiotensin system, the kallikrein kinin system, and type 2 diabetes mellitus. Investigations using transgenic and knock-out animal models--the results of which are also summarized--have improved our understanding of the interaction between endogenous fibrinolysis and endothelium. In each section of the review therapeutic implications and potentials are discussed.
Nordt
T K
TK
Medizinische Universitätsklinik Abt. Innere Medizin III (Kardiologie und Angiologie), Freiburg.
Bode
C
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D017073:Atherectomy; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005342:Fibrinolysis; D015870:Gene Expression; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010919:Placebos; D010958:Plasminogen / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000502:physiology; D010960:Plasminogen Activators / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010958:Plasminogen; D010960:Plasminogen Activators; D017257:Ramipril