Interrelationships between the fibrinolytic system and lipoproteins in the pathogenesis of coronary atherosclerosis

Abstract

The fibrinolytic system is comprised of a series of serine proteases and serine protease inhibitors which are involved in the dissolution of fibrin in the vascular lumen, but also in the migration of cells and in the remodeling of the extracellular matrix of the vascular wall. The transcription, expression and degradation of the various fibrinolytic enzymes by cells in the vascular wall is influenced by lipoproteins and this interrelationship may play a significant role in the development of the atherosclerotic plaque: the transcription of plasminogen activator inhibitor-1 is influenced by very low-density lipoproteins, the expression of both tissue plasminogen activator and plasminogen activator inhibitor-1 is influenced by low-density lipoproteins and lipoprotein(a) (Lp(a)) and the internalization of the urokinase: plasminogen activator inhibitor-1 complex occurs via the low-density lipoprotein related protein. Several clinical studies have shown correlations between fibrinolytic parameters and lipoproteins in healthy populations and in patients with dyslipidemia, but the correlation between single plasma fibrinolytic enzymes and the severity of coronary atherosclerosis is less well documented. The reduction of plasma lipids with lipid-lowering drugs also affects the concentration of fibrinolytic enzymes, although this may also be due to direct effects of the drugs on the expression of the various fibrinolytic enzymes. The reduction of fibrinolytic and proteolytic activity in the atherosclerotic plaque by their lipid-lowering effect and by their direct action on the fibrinolytic system may be one of the mechanisms by which some lipid-lowering drugs achieve plaque stabilization.