HYPOFIBRINOLYSIS AND THE INSULIN-RESISTANCE SYNDROME

Atherothrombosis seems now to be the most appropriate term to describe the pathogenic events leading to the development of cardiovascular di sease, An impaired fibrinolysis may not only contribute to and aggrava te the tendency to thrombosis but fibrin deposit may also play a role in the development of the atherosclerotic plaque. Hypofibrinolysis is observed among obese subjects and it has been shown that an excess of plasminogen activator inhibitor 1 (PAI 1) the main regulator of the fi brinolytic system, is closely associated to other components of the in sulin resistance syndrome, namely, excessive body weight, high waist t o hip ratio, elevated blood pressure, hyperinsulinemia and hypertrigly ceridemia. PAI 1 levels decrease with measures attempting at decreasin g insulin resistance, However, the mechanisms leading to increased PAI 1 levels are still unknown, On the basis of epidemiological studies, and in vitro studies with PAI secreting cells such as hepatocytes or e ndothelial cells, insulin, insulin precursors, and lipoproteins, mainl y VLDL, appear candidates for triggering this excessive secretion, but no definite answer has yet been found,