[Thrombotic tendency and laboratory medicine in metabolic syndrome]

Metabolic syndrome is defined as a complex of hypertriglyceride, insulin resistance, hypertension, and accumulation of visceral fat. This syndrome is often accompanied by thrombotic diseases (e.g., myocardial infarction, cerebral infarction), but the mechanism (s) of thrombotic tendency has not yet been elucidated. Plasminogen activator inhibitor-1 (PAI-1), a principal regulator of fibrinolytic system, plays a pathological role in the development of thrombosis and cardiovascular diseases. PAI-1 is regarded to be one of adipocytokines because it is produced and secreted by adipocytes. The expression of PAI-1 in adipocytes is upregulated by insulin, TNF-alpha, and TGF-beta, suggesting that it is relevant to insulin resistance. PAI-1 antigen level in plasma is elevated in obese subjects and increases in parallel with their BMI and visceral fat. It was experimentally revealed that PAI-1 expression in adipose tissue was dramatically increased in genetically obese mice and abundant expression of PAI-1 was localized to adipocytes in vivo. PAI-1 deficient mice were resistant to high fat diet-induced body weight gain, adipose accumulation, and insulin resistance in association with lack of decreased expression of adiponectin. Taken together, PAI-1 may be a key molecule to develop obesity and insulin resistance as well as thrombotic diseases. It is possible to prevent thrombotic complications and cardiovascular diseases in obese patients by controlling PAI-1 expression and function. Each pathology included in metabolic syndrome could stimulate PAI-1 expression, and thus, PAI-1 would be a good marker of progression of metabolic syndrome itself and of risk for thrombotic cardiovascular diseases as well.