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Thromb Haemost 2001; 86(05): 1305-1313
DOI: 10.1055/s-0037-1616066
DOI: 10.1055/s-0037-1616066
Review Article
Attenuation by Fibrates of Plasminogen Activator Inhibitor Type-1 Expression in Human Arterial Smooth Muscle Cells
Authors
This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG No214/2-1), by a grant-in-aid from the Medizinische Fakultät Heidelberg (148/95), and by a grant from the latter (178/97). The authors thank Stephanie Riester and Sandra Ernst for excellent technical assistance.
Further Information
Publication History
Received
01 March 2001
Accepted after resubmission
18 July 2001
Publication Date:
13 December 2017 (online)
Summary
Human atherosclerotic lesions exhibit increased expression of plasminogen activator inhibitor type-1 (PAI-1) that has been implicated in atherogenesis. Although vascular smooth muscle cells are a predominant source of PAI-1 expression potentially favorable modulation of PAI-1 expression by fibrates has not yet been characterized in these cells.
Human aortic smooth muscle cells were exposed to selected growth factors. PAI-1 expression was stimulated most powerfully by TGF-β (EC50 = 0.2 ng/ml, up to 12-fold increase). Gemfibrozil inhibited basal PAI-1 expression by 23% (p = ns) and TGF-β -induced PAI-1 expression by 52% (p = 0.017) whereas t-PA and total protein synthesis was not affected. Changes in PAI-1 protein accumulation reflected PAI-1 gene expression attributable to modulation of half-life of PAI-1 mRNA by gemfibrozil. Inhibition by other fibrates was less.
Gemfibrozil specifically attenuates TGF-β -induced PAI-1 expression in human arterial smooth muscle cells. Thus, fibrates are promising agents for normalizing increased PAI-1 expression in arterial walls in patients in whom PAI-1 expression is increased.
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References
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