TY - JOUR AU - Chandler, Wayne L TI - A Kinetic Model of the Circulatory Regulation of Tissue Plasminogen Activator SN - 0340-6245 SN - 2567-689X PY - 1991 JO - Thromb Haemost JF - Thrombosis and Haemostasis LA - EN VL - 66 IS - 09 SP - 321 EP - 328 DA - 2018/07/25 AB - A computer simulation was developed to study the regulation of active tissue plasminogen activator (t-PA) levels in plasma by kinetically modeling t-PA secretion, t-PA inhibition by plasminogen activator inhibitor type 1 (PAI-1), and hepatic clearance of t-PA, PAI-1 and t-PA/PAI-1 complex throughout a simplified human circulatory system. The model indicates that as the active PAI-1 concentration increases, the percent of t-PA in the active form decreases exponentially. Further, the reaction between t-PA and PAI-1 substantially reduces the half-lives of both active factors. By adjusting the t-PA and PAI-1 secretion rates to provide the best fit between simulated and measured circadian variations in t-PA, PAI-1 and complex, the model predicts that the diurnal rhythm in active t-PA levels is principally due to changes in the rate of PAI-1 secretion and not to variations in the t-PA secretion rate. In conclusion, the model predicts that PAI-1 is an important regulator of the concentration, half-life and circadian variation of active t-PA. PB - Schattauer GmbH DO - 10.1055/s-0038-1646415 UR - http://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1646415 ER -