Rerolle J P, Vigneau C, Hertig A, Berrou J, Rondeau E
Service de néphrologie A, INSERM U 489 et Association Claude Bernard, Hôpital Tenon, Paris.
Nephrologie. 2001;22(1):5-13.
Plasminogen activator inhibitor type 1 plays a prominent part in the regulation of extra and intra-vascular fibrinolysis through the inhibition of plasmin formation. In addition to its role in the resolution of blood clots, PAI-1 is involved in a variety of other biological processes including extracellular remodeling, cellular mobility, embryo implantation, development and tumoral proliferation. Moreover, PAI-1 is also implicated in various pathological processes such as thromboembolic diseases, atherosclerosis and fibrosis formation, particularly in the kidney and the lung. Inhibition of PAI-1 activity or of PAI-1 synthesis by specific antibodies, peptidic antagonists, antisens oligonucleotides or decoy oligonucleotides has been obtained in vitro but need to be evaluated in vivo. All these findings may have new therapeutical implications, explaining the importance of studies on PAI-1 production and regulation.
1型纤溶酶原激活物抑制剂通过抑制纤溶酶的形成,在血管外和血管内纤维蛋白溶解的调节中发挥重要作用。除了在血栓溶解中发挥作用外,PAI-1还参与多种其他生物学过程,包括细胞外重塑、细胞迁移、胚胎着床、发育和肿瘤增殖。此外,PAI-1还与各种病理过程有关,如血栓栓塞性疾病、动脉粥样硬化和纤维化形成,尤其是在肾脏和肺部。通过特异性抗体、肽拮抗剂、反义寡核苷酸或诱饵寡核苷酸抑制PAI-1活性或PAI-1合成已在体外实现,但需要在体内进行评估。所有这些发现可能具有新的治疗意义,这也解释了对PAI-1产生和调节进行研究的重要性。