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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Carotid Arteries, Carotid Stenosis, Cell Division, Connective Tissue, Disease Models, Animal, Hirudins, Immunohistochemistry, Ligation, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Plasminogen Activator Inhibitor 1, Prothrombin, Tunica Intima, Tunica Media, Vitronectin.
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Do plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model? Context: 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. 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.
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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. Final Decision: yes