Pai1

PAI-1, or plasminogen activator inhibitor-1, also known as SERPINE1, is a glycoprotein in the serpin (serine protease inhibitor) family that regulates fibrinolysis. It inhibits the serine proteases tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), thereby reducing the conversion of plasminogen to plasmin and slowing the degradation of fibrin. By limiting fibrinolysis, PAI-1 helps influence clot stability and the local remodeling of the extracellular matrix.

PAI-1 is primarily secreted by endothelial cells and adipocytes, but it is also produced by hepatocytes and platelets, and it circulates in plasma as well as in tissue compartments. In addition to its role in fibrinolysis, PAI-1 binds to fibrin, concentrating its inhibitory activity at sites of clots. The protein exists in active and latent conformations, with the latent form being inactive.

Expression of PAI-1 is tightly regulated by hormonal and metabolic signals, including insulin, glucocorticoids, inflammatory cytokines, and energy status. Plasma levels rise with obesity, insulin resistance, metabolic syndrome, and type 2 diabetes, and PAI-1 shows a circadian rhythm with higher morning levels.

Genetic variation in SERPINE1 influences PAI-1 expression. The best-studied promoter polymorphism is the 4G/5G insertion/deletion; the 4G allele is generally associated with higher PAI-1 levels and has been linked to cardiovascular and metabolic disease risk in some populations, though findings are not entirely consistent.

Clinically, elevated PAI-1 is associated with increased thrombosis risk, while deficiencies can cause bleeding tendencies. Because of its central role in fibrinolysis and tissue remodeling, PAI-1 is investigated as a potential therapeutic target in cardiovascular disease, fibrosis, and cancer.