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DOI: 10.1160/TH06-06-0321
Plasminogen activator inhibitor-1 impairs plasminogen activationmediated vascular smooth muscle cell apoptosis
Financial support: Patrick Rossignol received a grant from the Institut National de la Santé et de la Recherche Médicale (INSERM, France). This study was supported by the Leducq Foundation (Transatlantic Networks).Publikationsverlauf
Received
12. Juni 2006
Accepted after resubmission
14. September 2006
Publikationsdatum:
01. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200605/lookinside/thumbnails/10-1160-th06-06-0321-1.jpg)
Summary
The role of plasminogen activator inhibitor-1 (PAI-1) in vascular smooth muscle cell (VSMC) apoptosis mediated by plasminogen activation was studied with the use of aorticVSMC derived from mice with deficiency of PAI-1 (PAI-1-/-), tissue-type (t-PA-/-) or urokinase-type (u-PA-/-) plasminogen activator or from wildtype (WT) mice with corresponding genetic background. Plasminogen incubated with confluentVSMC was activated ina concentration-dependent and saturable manner for all four cell types, with maximal activation rates that were comparable for WT,u-PA-/and t-PA-/cells,but about two-fold higher for PAI-1-/cells. Plasminogen activation was impaired by addition of the lysine analogue 6-aminohexanoic acid, and by addition of t-PA and u-PA neutralizing antibodies, suggesting that it depends on binding to cell surface COOH-terminal lysine residues, and on plasminogen activator activity. Morphological alterations consistent with apoptosis were observed much earlier in PAI-1-/than in WT VSMC. Without addition of plasminogen, the apoptotic index was similar for all four cell types, whereas after incubation with physiological plasminogen concentrations, it was greater in PAI-1-/VSMC, as compared to WT, t-PA-/or u-PA-/VSMC. Furthermore, the apoptotic rate paralleled the release of plasmin. Thus, plasmin-mediated apoptosis of VSMC occurs via plasminogen activation by either t-PA or u-PA and is impaired by PAI-1.
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