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• W2039345230 abstract "Introduction: We determined the role of smooth muscle cell (SMC)-derived plasminogen activator inhibitor-1 (PAI-1) in the flow-induced SMC migratory response. Materials and methods: Wild type (wt) or PAI-1 knockout SMC were cultured in the absence or presence of endothelial cells (EC) under static or pulsatile flow conditions in a perfused culture system. SMC migration was then assessed by Transwell assay. Results: Pulsatile flow significantly increased SMC PAI-1 mRNA and protein levels, ∼4- and 3-fold respectively (n=4, p<0.05). In the absence, but not in the presence of EC, pulsatile flow significantly increased (∼2.4-fold) the migration of wt SMC when compared to wt SMC cultured under static conditions. PAI-1 −/−SMC migration was significantly increased under flow conditions as compared to wild-type controls (334±22% vs. 237±11%, n=6, p<0.05). This flow-induced migration was significantly attenuated, but not completely inhibited, when PAI-1 −/−SMC were cultured in the presence of EC (147±13%, n=6, p<0.05). The flow-induced PAI-1 −/−SMC migratory response was partially inhibited by an anti-urokinase plasminogen activator (uPA) antibody (#1189), and completely inhibited by both 1189 and the matrix metalloproteinase (MMP) inhibitor BB3103. In parallel PAI-1 −/−SMC cells, there was a greater flow-induced increase in proMMP-2 activity as compared to wild-type control cells. Moreover, under both static and flow conditions, tissue inhibitors of matrix metalloproteinases (TIMP)-2 activity was reduced in these PAI-1-deficient cells as compared to wild-type controls. Conclusions: These results suggest that SMC PAI-1 plays a role in limiting flow-induced SMC migration and thus may be an important mechanism for controlling the process of vascular remodelling." @default.
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• W2039345230 date "2004-01-01" @default.
• W2039345230 modified "2023-10-14" @default.
• W2039345230 title "Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle cell migration" @default.
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• W2039345230 doi "https://doi.org/10.1016/j.thromres.2004.05.003" @default.
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