Plasminogen Activator Inhibitor-1 in the Pathogenesis of Asthma

Abstract

Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and is known to play an essential role in tissue remodeling. Recent evidence indicates that chronic asthma may lead to tissue remodeling such as subepithelial fibrosis and extracellular matrix (ECM) deposition in the airways. However, the role of PAI-1 in asthma is unknown. Recently the mast cell (MC), which plays a major role in asthma, was found as a novel source of PAI-1, and a large number of MCs expressing PAI-1 are infiltrated in the airways of patients with severe asthma. Furthermore, PAI-1-deficient mice show reduced ECM deposition in the airways of a murine model of chronic asthma by inhibiting MMP-9 activity and fibrinolysis. In a human study, the 4G allele frequency was significantly higher in the asthmatic patients than in the control group. In view of the findings that the 4G allele is associated with elevated plasma PAI-1 level, elevated PAI-1 level in the lung may contribute to the development of asthma. In summary, PAI-1 may play an important role in the pathogenesis of asthma and further studies evaluating the mechanisms of PAI-1 action may lead to the development of a novel therapeutic target for the treatment and prevention of asthma.