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Thromb Haemost 2002; 87(03): 523-529
DOI: 10.1055/s-0037-1613034
Review Article
Schattauer GmbH

15 Deoxy Δ12,14 PGJ2 Induces Procoagulant Activity in Cultured Human Endothelial Cells

Shaoping Xie
1   Thrombosis Research Institute, Emmanuel Kaye Building, London, UK
,
David J. O’Regan   *
1   Thrombosis Research Institute, Emmanuel Kaye Building, London, UK
,
Vijay V. Kakkar
1   Thrombosis Research Institute, Emmanuel Kaye Building, London, UK
,
Michael F. Scully
1   Thrombosis Research Institute, Emmanuel Kaye Building, London, UK
› Author Affiliations
Further Information

Publication History

Received 28 May 2001

Accepted after revision 13 December 2001

Publication Date:
14 December 2017 (online)

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Summary

15 deoxy Δ12,14 PGJ2 (15d-PGJ2), a high affinity ligand of peroxisome proliferator-activated receptor γ (PPAR γ has been proposed to act as a negative feedback regulator of the inflammatory response. We investigated the effect of 15d-PGJ2 on the anticoagulant property of endothelial cells. 15d-PGJ2 stimulated a moderate but sustained increase in tissue factor (TF) activity in HUVECs and EA.hy926 cells while causing a partial loss of thrombomodulin (TM) activity. When cells were co-treated with 15d-PGJ2 and TNF-α, the subsequent elevation of TF activity was synergistically increased over that of cells treated with TNF-α, alone and the decline of TF activity after 24 h was less marked than TNF-α, alone. The induction of TF by 15d-PGJ2 alone and in combination with TNF-α, was reduced in the presence of PD 98059, suggesting the participation of the MEK/ERK pathway. The thiazolidinedione PPAR γ agonist ciglitazone had no effect on TF levels but reduced the expression of endothelial protein C receptor. The ability of 15d-PGJ2 to enhance a procoagulant phenotype arising from TNF-α, suggests a pro-inflammatory role for the prostaglandin.

Keywords

15 deoxy Δ12,14 PGJ2 - peroxisome proliferator-activated receptor γ - tissue factor - thrombomodulin - endothelial cells

* Present address: Dr. D. J. O’Regan, Department of Cardiac Surgery, General Infirmary, Leeds, UK


 

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