PLAT and liver disorder: These data are consistent with several recent studies showing that; 1) direct manipulation of plasmin/PAI-1 with adenovirus-mediated transfer of siRNA decreased hepatic fibrosis in dimethylnitrosamine-induced and bile duct ligation-induced liver disease models [30]; 2) restoration of hepatic plasmin activity by a mutant, noninhibitory PAI-1 was also associated with decreased fibrotic matrix accumulation in this model [31] and, 3) higher levels of tPA activation have been associated with fewer hepatic lesions in PAI-1 (−/−) mice [32].