This Article Full Text Full Text (PDF) All Versions of this Article: 96/1/e1    most recent 01.RES.0000153150.27690.f2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rabausch, K. Articles by Weber, A.-A. Search for Related Content PubMed PubMed Citation Articles by Rabausch, K. Articles by Weber, A.-A.

(Circulation Research. 2005;96:e1.)
© 2005 American Heart Association, Inc.

UltraRapid Communication

Regulation of Thrombomodulin Expression in Human Vascular Smooth Muscle Cells by COX-2–Derived Prostaglandins

Kerstin Rabausch, Ellen Bretschneider, Mario Sarbia, Jutta Meyer-Kirchrath, Petra Censarek, Robert Pape, Jens W. Fischer, Karsten Schrör, Artur-Aron Weber

From the Institut für Pharmakologie und Klinische Pharmakologie (K.R., J.M.-K., P.C., R.P., J.W.F., K.S., A.-A.W.), Universitätsklinikum Düsseldorf, Germany; Zentrum für Vaskuläre Biologie und Medizin (E.B.), Universität Jena, Germany; and Institut für Pathologie (M.S.), Technische Universität München, Munich, Germany.

Correspondence to Artur-Aron Weber, MD, Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. E-mail weberar{at}uni-duesseldorf.de

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.

Key Words: cyclooxygenase • prostaglandins • thrombomodulin • smooth muscle cells • thrombosis

This article has been cited by other articles:

				A. C. Rosenkranz, B. H. Rauch, K. Freidel, and K. Schror Regulation of protease-activated receptor-1 by vasodilatory prostaglandins via NFAT Cardiovasc Res, September 1, 2009; 83(4): 778 - 784. [Abstract] [Full Text] [PDF]

				F. Seta, A. D. Chung, P. V. Turner, J. D. Mewburn, Y. Yu, and C. D. Funk Renal and cardiovascular characterization of COX-2 knockdown mice Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1751 - R1760. [Abstract] [Full Text] [PDF]

				M. M. Bertagnolli, A. G. Zauber, and S. Solomon Prostaglandin Inhibition and Cardiovascular Risk: Maybe Timing Really Is Everything Cancer Prevention Research, March 1, 2009; 2(3): 195 - 196. [Full Text] [PDF]

				I.-C. Lo, T.-M. Lin, L.-H. Chou, S.-L. Liu, L.-W. Wu, G.-Y. Shi, H.-L. Wu, and M. J. Jiang Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin expression in human vascular smooth muscle cells Cardiovasc Res, March 1, 2009; 81(4): 771 - 779. [Abstract] [Full Text] [PDF]

				L. Di Francesco, L. Totani, M. Dovizio, A. Piccoli, A. Di Francesco, T. Salvatore, A. Pandolfi, V. Evangelista, R. A. Dercho, F. Seta, et al. Induction of Prostacyclin by Steady Laminar Shear Stress Suppresses Tumor Necrosis Factor-{alpha} Biosynthesis via Heme Oxygenase-1 in Human Endothelial Cells Circ. Res., February 27, 2009; 104(4): 506 - 513. [Abstract] [Full Text] [PDF]

				K. Brune, H. A. Katus, J. Moecks, E. Spanuth, A. S. Jaffe, and E. Giannitsis N-Terminal Pro-B-Type Natriuretic Peptide Concentrations Predict the Risk of Cardiovascular Adverse Events from Antiinflammatory Drugs: A Pilot Trial Clin. Chem., July 1, 2008; 54(7): 1149 - 1157. [Abstract] [Full Text] [PDF]

				R. Pape, B. H. Rauch, A. C. Rosenkranz, G. Kaber, and K. Schror Transcriptional Inhibition of Protease-Activated Receptor-1 Expression by Prostacyclin in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 534 - 540. [Abstract] [Full Text] [PDF]

				W. B. White Cardiovascular Effects of the Cyclooxygenase Inhibitors Hypertension, March 1, 2007; 49(3): 408 - 418. [Full Text] [PDF]

				E. Bretschneider, B. Uzonyi, A.-A. Weber, J. W. Fischer, R. Pape, K. Lotzer, and K. Schror Human Vascular Smooth Muscle Cells Express Functionally Active Endothelial Cell Protein C Receptor Circ. Res., February 2, 2007; 100(2): 255 - 262. [Abstract] [Full Text] [PDF]

				J.-J. Stampfuss, P. Censarek, J. W. Fischer, K. Schror, and A.-A. Weber Rapid Release of Active Tissue Factor From Human Arterial Smooth Muscle Cells Under Flow Conditions Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): e34 - e37. [Abstract] [Full Text] [PDF]

				E. Fosslien Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385. [Abstract] [Full Text] [PDF]

				M. Hermann, H. Krum, and F. Ruschitzka To the Heart of the Matter: Coxibs, Smoking, and Cardiovascular Risk Circulation, August 16, 2005; 112(7): 941 - 945. [Full Text] [PDF]