Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner. Adipocyte-derived PAI-1, predominantly expressed in visceral fat, is released into the circulation in parallel with increased fat mass, and it functions as a crucial adipokine that negatively affects physiological metabolism and vascular biology. Elevated PAI-1 levels induce insulin resistance and metabolic abnormalities during proinflammatory processes involving several cytokines and chemokines in diabetes. Several studies have indicated that PAI-1 plays crucial roles in insulin actions on liver, muscle, and fat. Accumulated fat and enhanced adipose tissue-derived PAI-1 influence metabolism and vessels in relation to macrophage infiltration, chronic inflammation, and free fatty acid release in obese states. PAI-1-induced fibrinolysis abnormalities are associated with metabolic syndrome, leading to cardiovascular disease through dysregulated vascular coagulation, endothelial dysfunction, and metabolic abnormalities. Adipose tissue-derived PAI-1 is involved in insulin resistance, osteoporosis, and sarcopenia induced by glucocorticoid excess in mice. Moreover, PAI-1 is involved in the other pathological states, such as nonalcoholic fatty liver disease, and cancer. As such, PAI-1 may be exploited as a marker of disease activity as well being a target for clinical drug development. © 2016 American Physiological Society. Compr Physiol 6:1873-1896, 2016.
Copyright © 2016 John Wiley & Sons, Inc.