Plasma plasminogen activator inhibitor 1, insulin resistance and android obesity

Plasma plasminogen activator inhibitor 1 (PAI-1) levels are elevated in insulin-resistant subjects and are associated with increased cardiovascular risk of atherothrombosis. Strong association between PAI-1 and the metabolic components of the insulin resistance syndrome is found in clinical studies, suggesting that insulin resistance may regulate circulating PAI-1. However, the mechanisms underlying increased PAI-1 levels in such conditions are still poorly understood. Several studies have been carried out specifically in patients with central or android obesity, a major characteristic of the insulin resistance syndrome, and have suggested that visceral adipose tissue may be the major component of the relationship between android obesity and PAI-1. Accordingly, adipose tissue PAI-1 production was found to be elevated in obese human subjects, particularly in visceral adipose tissue. The genetic background for having high PAI-1 levels in several populations have been looked for and its role appeared to be weaker than that of the metabolic condition. High plasma PAI-1 levels are then clearly related to android obesity and insulin resistance, but the mechanisms whereby PAI-1 increases in plasma in these diseases remain to be determined.