Successful silencing of plasminogen activator inhibitor-I in human vascular enclothelial cells using small interfering RNA
2006 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Successful silencing of plasminogen activator inhibitor-I in human vascular enclothelial cells using small interfering RNA
Hecke, A.; Brooks, H.; Meryet-Figuiere, M.; Minne, S.; Konstantinides, S.; Hasenfuß, G. & Lebleu, B. et al. (2006)
Thrombosis and Haemostasis, 95(5) pp. 857-864. DOI: https://doi.org/10.1160/TH05-08-0569
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- Authors
- Hecke, A.; Brooks, H; Meryet-Figuiere, M; Minne, S.; Konstantinides, Stavros; Hasenfuß, Gerd ; Lebleu, B.; Schäfer, Katrin
- Abstract
- Clinical as well as experimental evidence suggests that vascular overexpression of plasminogen activator inhibitor (PAI)-1, the primary physiological inhibitor of both urokinase and tissue-type plasminogen activator, may be involved in the pathophysiology of atherosclerosis and cardiovascular disease. We investigated the feasibility, efficacy and functional effects of PAI-1 gene silencing in human vascular endothelial cells using small interfering RNA. Double-stranded 21 bp-RNA molecules targeted at sequences within the human PAI-1 gene were constructed. Successful siRNA transfection of HUVEC was confirmed using fluorescence microscopy and flow cytometry. One of five candidate siRNA sequences reduced PAI-1 mRNA and protein in a concentration- and time-dependent manner. Suppression of PAI-1 mRNA was detected up to 72 hours after transfection. Moreover, siRNA treatment reduced the activity of PAI-1 released from HUVEC,and prevented the oxLDL- or LPS-induced upregulation of PAI-1 secretion. Importantly, siRNA treatment did not affect the expression of other endothelial-cell markers. Moreover, downregulation of PAI-1 significantly enhanced the ability of endothelial cells to adhere to vitronectin,and this effect could be reversed upon addition of recombinant PAI-1. SiRNA-mediated reduction of PAI-1 expression may be a promising strategy for dissecting the effects of PAI-1 on vascular homeostasis.
- Issue Date
- 2006
- Journal
- Thrombosis and Haemostasis
- ISSN
- 0340-6245