Fibrinolytic function and coronary risk.
Plasminogen activation potential in the blood is controlled by an equilibrium between plasminogen activators, mainly tissue-type plasminogen activator (t-PA), and inhibitors, mainly plasminogen activator inhibitor (PAI)-1. In cardiovascular practice, imbalance of this fibrinolytic potential is encountered primarily in the insulin-resistance syndrome. This syndrome leads to increased plasma PAI-1 and t-PA antigen levels (reflecting inactive t-PA/PAI-1 complexes) with a consequent decrease in fibrinolytic activity. Increased plasma PAI-1 and t-PA antigen both are predictive of myocardial infarction. The prognostic value of PAI-1 disappears after adjustments for insulin resistance markers, whereas the prognostic value of t-PA antigen disappears after simultaneous adjustments for insulin resistance and inflammation markers, suggesting an additive role of inflammation in inducing plasma fibrinolytic markers. Recently the production of PAI-1 by adipose tissue, in particular by tissue from the omentum, has been shown. PAI-1 produced in this way could be an important contributor to the elevated plasma PAI-1 levels observed in insulin-resistant patients. These results support the notion that PAI-1 may be a link between obesity, insulin resistance, and cardiovascular disease. Genetic control of PAI-1 expression has also been shown, involving a -675 4G/5G polymorphism, the 4G/4G genotype being associated with higher plasma PAI-1 levels; its proper influence on the development of myocardial infarction is still debated.
Juhan-Vague
I
I
Laboratoire d'Hématologie, CHU Timone, 13385 Marseille, France.
Morange
P
P
Christine Alessi
M
M
D003327:Coronary Disease / Q000209:etiology* / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator