Angiotensin and vascular fibrinolytic balance.
Fibrinolysis is controlled by the plasminogen activator system. The proteolytic activity of this system is mediated by plasmin, which is generated from plasminogen by one of two plasminogen activators. Plasminogen activator inhibitor-1 (PAI-1) inhibits this process. Individuals with reduced fibrinolytic activity are at increased risk for ischemic cardiovascular events, and reduced fibrinolysis may underlie some of the pathological consequences of reduced nitric oxide (NO) availability. Within the vasculature, angiotensin II stimulates the release of PAI-1, thereby reducing fibrinolytic activity. Thus, the plasminogen activator system is largely controlled by the renin-angiotensin system (RAS). In accordance with this finding, treatment with angiotensin converting enzyme (ACE) inhibitors is associated with substantial reductions in the incidence of ischemic cardiovascular events. Links between the RAS, fibrinolytic balance, and cardiovascular pathology are further supported by evidence from transgenic and knockout animal models. This article discusses the role of the plasminogen activator system in cardiovascular pathology, and the potential for alleviating that pathology by manipulation of the RAS.
Vaughan
Douglas E
DE
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6300, USA. doug.vaughan@mcmail.vanderbilt.edu
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D009569:Nitric Oxide; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator