Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model.
OBJECTIVE: We previously reported that plasminogen activator inhibitor 1 ( PAI-1), in the presence of vitronectin ( VN), inhibits thrombin activity in vitro. Furthermore, we demonstrated in human atherosclerotic plaques the colocalization of thrombin, PAI-1, and VN, as well as activity of thrombin and PAI-1. Here, we show that PAI-1 is a local thrombin inhibitor in vivo. METHODS AND RESULTS: We used the murine carotid artery ligation model to assess the role of PAI-1 and VN in stenosis by using PAI-1-deficient ( PAI-1(-/-)) and VN(-/-) mice. Ligation resulted in a smooth muscle cell (SMC)-rich intima without infiltrating cells. We show that PAI-1(-/-) and VN(-/-) mice generate a larger intima than wild-type mice as the result of more extensive SMC proliferation, as evidenced by cell counting and staining for proliferating cell-nuclear antigen. CONCLUSIONS: In PAI-1(-/-) mice, excessive intima formation is prevented by the thrombin-specific inhibitor hirudin. Finally, immunohistochemical analysis revealed PAI-1, VN, and (pro)thrombin antigen in intimal lesions. Our observations are compatible with inhibition of thrombin-mediated SMC proliferation by PAI-1/ VN complexes.[1]References
- Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model. de Waard, V., Arkenbout, E.K., Carmeliet, P., Lindner, V., Pannekoek, H. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
