Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins.
There is concern that cyclooxygenase (COX)-2 inhibitors may promote atherothrombosis by inhibiting vascular formation of prostacyclin (PGI2) and an increased thrombotic risk of COX-2 inhibitors has been reported. It is widely accepted that the prothrombotic effects of COX-2 inhibitors can be explained by the removal of platelet-inhibitory PGI2. Using microarray chip technology, we have previously demonstrated that thrombomodulin (TM) mRNA is upregulated in cultured human coronary artery smooth muscle cells by the stable prostacyclin mimetic iloprost. This study is the first to demonstrate a stimulation of the expression of functionally active thrombomodulin in human smooth muscle cells by prostaglandins, endogenously formed via the COX-2 pathway. Because TM is an important inhibitor of blood coagulation, these findings provide a novel platelet-independent mechanism to explain the prothrombotic effects of COX-2 inhibitors. The full text of this article is available online at http://circres.ahajournals.org.
Rabausch
Kerstin
K
Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany.
Bretschneider
Ellen
E
Sarbia
Mario
M
Meyer-Kirchrath
Jutta
J
Censarek
Petra
P
Pape
Robert
R
Fischer
Jens W
JW
Schrör
Karsten
K
Weber
Artur-Aron
AA
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D016895:Culture Media, Serum-Free; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007546:Isoquinolines; D008565:Membrane Proteins; C545647:PTGER3 protein, human; D011453:Prostaglandins; D011725:Pyridines; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides; D013450:Sulfones; D018180:Thrombomodulin; D014665:Vasodilator Agents; D004008:Diclofenac; D005576:Colforsin; D003994:Bucladesine; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000527:Alprostadil; C048491:butaprost; D016285:Iloprost; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C043867:cicaprost; D013755:Tetradecanoylphorbol Acetate; D000077613:Etoricoxib