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Thromb Haemost 2005; 94(01): 46-52
DOI: 10.1160/TH04-10-0661
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Modulation of tissue factor expression by rapamycin and FK-506 in lipopolysaccharide-stimulated human mononuclear cells and serum-stimulated aortic smooth muscle cells

Véronique Ollivier
1   INSERM U479, Faculté Xavier Bichat, Paris, France
,
Soumeya Hammal
1   INSERM U479, Faculté Xavier Bichat, Paris, France
,
Nejma Ameziane
1   INSERM U479, Faculté Xavier Bichat, Paris, France
2   Hôpital Louis Mourier, AP-HP, Colombes, France
,
Marie-Thérèse Labro
1   INSERM U479, Faculté Xavier Bichat, Paris, France
,
Dominique de Prost
1   INSERM U479, Faculté Xavier Bichat, Paris, France
2   Hôpital Louis Mourier, AP-HP, Colombes, France
› Author Affiliations
Further Information

Publication History

Received 12 October 2004

Accepted after resubmission 03 May 2005

Publication Date:
05 December 2017 (online)

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Summary

Inflammation is a key pathogenic component of atherosclerosis; it also promotes thrombosis, a process underlying acute coronary events and stroke. Cells present in atherosclerotic plaque show abnormal tissue factor (TF) expression. Macrolides, in addition to their antimicrobial properties, have antiinflammatory effects that might help prevent atherothrombosis. The aim of this study was to determine the effect of an immunosuppressant macrolide, rapamycin (Sirolimus), on the expression of TF and its inhibitor (TFPI) by monocytic cells (human blood mononuclear and THP-1 cells) and human aortic smooth muscle cells, in comparison with FK-506 and azithromycin. In monocytic cells, rapamycin and FK-506 inhibited LPS-induced TF activity, antigen and mRNA expression through a transcriptional mechanism involving NF-κB. In smooth muscle cells, rapamycin and azithromycin had no effect on serum-induced TF expression, while FK-506 increased serum-induced TF protein and mRNA expression. TFPI levels in the culture supernatants of serum-stimulated smooth muscle cells were not modified by any of the three macrolides. Rapamycin slightly inhibits TFPI induction by LPS in monocytic cells. In addition to its recently established efficacy in the prevention of stent restenosis, the inhibitory effect of rapamycin on theTF pathway might have interesting therapeutic implications.

Keywords

Rapamycin - monocytes - smooth muscle cells - tissue factor - macrolide
 

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