title: Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins.
abstract: 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.
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rabausch
authors.forename: Ellen
authors.initials: E
authors.lastname: Bretschneider
authors.forename: Mario
authors.initials: M
authors.lastname: Sarbia
authors.forename: Jutta
authors.initials: J
authors.lastname: Meyer-Kirchrath
authors.forename: Petra
authors.initials: P
authors.lastname: Censarek
authors.forename: Robert
authors.initials: R
authors.lastname: Pape
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
authors.forename: Artur-Aron
authors.initials: AA
authors.lastname: Weber
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000473:pathology; D002343:Carotid Artery, Internal / Q000737:chemistry / Q000201:enzymology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology; D016895:Culture Media, Serum-Free; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077613:Etoricoxib; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008323:Mammary Arteries / Q000166:cytology; D008565:Membrane Proteins; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011453:Prostaglandins / Q000172:deficiency; D011725:Pyridines / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012501:Saphenous Vein / Q000166:cytology; D015290:Second Messenger Systems / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018180:Thrombomodulin / Q000096:biosynthesis* / Q000235:genetics; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: 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