Fibrinolytic balance, the renin-angiotensin system and atherosclerotic disease

The plasminogen activator or fibrinolytic system is an important determinant of vascular homeostasis. It is one of the endogenous defence mechanisms against intravascular thrombus formation, which is implicated in the pathogenesis of myocardial infarction and other acute coronary syndromes. Reduced fibrinolytic activity is a risk factor for ischaemic cardiovascular events. The fibrinolytic system also contributes prominently to vascular remodelling. Fibrinolysis depends on a balance between plasminogen activators, such as urokinase and tissue-type plasminogen activator. and plasminogen activator inhibitor type 1. A growing body of evidence indicates that the renin-angiotensin system can disrupt the equilibrium of the fibrinolytic system both directly and indirectly, with clinical consequences. For example, it appears that angiotensin II and angiotensin IV increase the expression of plasminogen activator inhibitor type 1. Pharmacological interruption of the renin-angiotensin system with inhibitors of angiotensin-converting enzyme (ACE) exerts a positive influence on endogenous fibrinolytic balance by blocking the formation of angiotensin II and preventing the degradation of bradykinin. Recent data from our laboratory have provided additional evidence for a link between the renin-angiotensin system and the fibrinolytic system. These findings may help elucidate possible mechanisms by which ACE inhibition exerts vasculoprotective effects and reduces the risk of atherothrombotic events.