The endogenous fibrinolytic system is under meticulous control of clot-dissolving enzymes such as t-PA and inhibitors of these enzymes, such as PAI-1. This system represents the most studied of the anticoagulant systems regarding future cardiovascular risk.
PAI-1 is produced in the human vascular endothelial cell, the liver, and adipose tissue (68). PAI-1 is a serine protease that binds and irreversibly inhibits tPA from cleaving fibrin. Several genetic polymorphisms of PAI-1 have been identified, the most studied of which is a 4G/5G insertion/deletion polymorphism located in the promoter region of the gene (69). This polymorphism is associated with plasma levels of PAI-1 (70) and may also be related to the prothrombotic environment associated with insulin resistance in several populations (71-74). A meta-analysis of nine studies evaluating this PAI-1 polymorphism among more than 1500 cases and controls found a small increase, most pronounced in high-risk populations, in the outcome of MI with the mutation (75).
Prospective studies evaluating the predictive risk associated with increased plasma PAI-1 levels have been performed. In patients with acute ST-elevation MI, PAI-1 levels correlate with mortality (76). In young patients who survive MI, high PAI-1 levels have been reported in association with hypertriglyceridemia (77). Finally, in patients without a previous MI, increased PAI-1 levels in men were found to correlate with future MI (78). Future studies must consider carefully the independent prognostic value of PAI-1 levels above current clinical risk factors. A special emphasis should continue on patient populations with insulin resistance and metabolic syndrome.
Was this article helpful?
Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...