Reference : The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent
Devy, L. [> > > >]
Blacher, Silvia mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Grignet-Debrus, Christine mailto [Université de Liège - ULg > Services administratifs généraux > Protection et hygiène du travail (SUPHT) >]
Bajou, Khalid mailto [Université de Liège - ULg > Département des sciences de la vie > Biologie et génétique moléculaire >]
Masson, Véronique [Centre Hospitalier Universitaire de Liège - CHU > > Gynécologie-Obstétrique CHR >]
Gerard, R. D. [> > > >]
Gils, A. [> > > >]
Carmeliet, G. [> > > >]
Carmeliet, P. [> > > >]
Declerck, P. J. [> > > >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
FASEB Journal
Federation of American Society for Experimental Biology
Yes (verified by ORBi)
[en] angiogenesis ; cell migration ; proteolysis ; serine protease ; PAI-1
[en] Plasminogen activator inhibitor 1 (PAI-1) is believed to control proteolytic activity and cell migration during angiogenesis. We previously demonstrated in vivo that this inhibitor is necessary for optimal tumor invasion and vascularization. We also showed that PAI-1 angiogenic activity is associated with its control of plasminogen activation but not with the regulation of cell-matrix interaction. To dissect the role of the various components of the plasminogen activation system during angiogenesis, we have adapted the aortic ring assay to use vessels from gene-inactivated mice. The single deficiency of tPA, uPA, or uPAR, as well as combined deficiencies of uPA and tPA, did not dramatically affect microvessel formation. Deficiency of plasminogen delayed microvessel outgrowth. Lack of PAI-1 completely abolished angiogenesis, demonstrating its importance in the control of plasmin-mediated proteolysis. Microvessel outgrowth from PAI-1(-/-) aortic rings could be restored by adding exogenous PAI-1 (wild-type serum or purified recombinant PAI-1). Addition of recombinant PAI-1 led to a bell-shaped angiogenic response clearly showing that PAI-1 is proangiogenic at physiological concentrations and antiangiogenic at higher levels. Using specific PAI-1 mutants, we could demonstrate that PAI-1 promotes angiogenesis at physiological (nanomolar) concentrations through its antiproteolytic activity rather than by interacting with vitronectin.

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