Targeted gene manipulation and transfer of the plasminogen and coagulation systems in mice

The blood coagulation and the fibrinolytic (or plasminogen/plasmin) systems determine the balance between the formation and dissolution of blood clots, but also contribute to the pathogenesis of various cardiovascular disorders such as thrombosis, atherosclerosis, and restenosis. Furthermore, they participate in a variety of other (patho)biological processes such as embryonic development, reproduction, wound healing, cancer, and brain function. Two recently developed technologies, gene targeting and gene transfer, which allow the manipulation of the genetic balance of these proteinase systems in a controllable manner, have resulted in a clearer elucidation of the biological role of these systems. This review summarizes the insights that have been obtained from the gene targeting studies and discusses the use of adenovirus-mediated transfer of fibrinolytic genes to study and the possibility of developing novel strategies for the treatment of restenosis and thrombosis.