(Circulation. 1997;95:1870-1876.)
© 1997 American Heart Association, Inc.
Articles |
Different Effects of Thrombin Receptor Activation on Endothelium and Smooth Muscle Cells of Human Coronary Bypass Vessels
Implications for Venous Bypass Graft Failure
Presented in part at the 67th Annual Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
From the Departments of Cardiology, Cardiovascular Research (Z.Y., F.R., G.N., F.J., H.J., V.G., T.F.L.), and Cardiovascular and Thoracic Surgery (U.A.), University Hospital, Inselspital Bern, Switzerland; the Department of Nephrology and Hypertension (T.J.R.), University Hospital Utrecht, Netherlands; and the Department of Heart and Thoracic Surgery (I.A.), University Hospital, Göttingen, Germany.
Correspondence to Thomas F. Lüscher, MD, Professor of Medicine, Cardiology, Cardiovascular Research, University Hospital, Rämistrasse 100, CH-8091, Zürich, Switzerland.
Background Thrombin is implicated in coronary bypass graft disease; it cleaves its receptor's extracellular N-terminal domain and unmasks a new N-terminus as a tethered ligand. We studied the effects of thrombin receptor activation in human internal mammary artery (IMA) and saphenous vein (SV).
Methods and Results To study the effects of thrombin receptor activation on vasomotion, isolated blood vessels were suspended for isometric tension recording, and the effects on cell proliferation were studied in cultured smooth muscle cells (SMCs) of IMA and SV. Thrombin receptor expression in IMA and SV was analyzed by reverse transcription polymerase chain reaction and immunohistology. Receptor function was studied by analyzing the activation of mitogen-activated protein kinase (p42MAPK). In IMA thrombin evoked endothelium-dependent relaxations (65±5%) that were mimicked by thrombin receptor agonist peptide (TRAP) and reduced by the thrombin inhibitors recombinant (r-) hirudin and D-Phe-Pro-Arg-chloromethyl ketone (PPACK) (P<.05). In SV thrombin caused contractions (36±5% of 100 mmol/L KCl) that were inhibited by r-hirudin or PPACK (P<.05) but not mimicked by TRAP. In SMCs thrombin induced more pronounced [3H]thymidine incorporation (inhibited by r-hirudin or PPACK) in SV than IMA (P<.05), but activation of p42MAPK was similar in both vessels. TRAP induced weaker activation of p42MAPK than thrombin and did not stimulate [3H]thymidine incorporation in SMCs of SV or IMA. Immunohistology and RT-PCR demonstrated that the endothelium and SMCs of IMA and SV express thrombin receptor.
Conclusions Functional thrombin receptors are present on endothelium and SMCs of IMA and SV. Endothelial thrombin receptors mediate relaxation in IMA but not SV. Thrombin causes much more pronounced contraction and proliferation in SMCs of SV than IMA independent of tethered receptors, suggesting other thrombin receptors exist. These differences of thrombin receptor activation in IMA and SV may be important in the development of and therapy for graft disease.
Key Words: arteries • veins • receptors • grafting
This article has been cited by other articles:
 |
|
 |
|
  S.K. Payeli, R. Latini, C. Gebhard, A. Patrignani, U. Wagner, T.F. Luscher, and F.C. Tanner Prothrombotic Gene Expression Profile in Vascular Smooth Muscle Cells of Human Saphenous Vein, but Not Internal Mammary Artery Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 705 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Gigante, A. Bellis, R. Visconti, M. Marino, C. Morisco, V. Trimarco, G. Galasso, F. Piscione, N. De Luca, J. A. Prince, et al. Retrospective Analysis of Coagulation Factor II Receptor (F2R) Sequence Variation and Coronary Heart Disease in Hypertensive Patients Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1213 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gaudino, N. Luciani, F. Glieca, C. Cellini, C. Pragliola, C. Trani, F. Burzotta, G. Schiavoni, A. Anselmi, and G. Possati Patients with in-stent restenosis have an increased risk of mid-term venous graft failure. Ann. Thorac. Surg., September 1, 2006; 82(3): 802 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. de Waard, E. K. Arkenbout, M. Vos, A. I.M. Mocking, H. W.M. Niessen, W. Stooker, B. A.J.M. de Mol, P. H.A. Quax, E. N.T.P. Bakker, E. VanBavel, et al. TR3 Nuclear Orphan Receptor Prevents Cyclic Stretch-Induced Proliferation of Venous Smooth Muscle Cells Am. J. Pathol., June 1, 2006; 168(6): 2027 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Barandier, J.-P. Montani, and Z. Yang Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1807 - H1813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tabuchi, M. Shichiri, A. Shibamiya, T. Koyama, F. Nakazawa, J. Chung, S. Hirosawa, and M. Sunamori Non-viral in vivo thrombomodulin gene transfer prevents early loss of thromboresistance of grafted veins Eur. J. Cardiothorac. Surg., November 1, 2004; 26(5): 995 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chilov, C. Fux, H. Joch, and M. Fussenegger Identification of a novel proliferation-inducing determinant using lentiviral expression cloning Nucleic Acids Res., September 15, 2003; 31(18): e113 - e113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bobe, X. Yin, M.-C. Roussanne, O. Stepien, E. Polidano, C. Faverdin, and P. Marche Evidence for ERK1/2 activation by thrombin that is independent of EGFR transactivation Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H745 - H754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Bosnjak, K. Terata, H. Miura, A. Sato, A. C. Nicolosi, M. McDonald, S. A. Manthei, T. Saito, O. A. Hatoum, and D. D. Gutterman Mechanism of thrombin-induced vasodilation in human coronary arterioles Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1080 - H1086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pajusola, M. Gruchala, H. Joch, T. F. Luscher, S. Yla-Herttuala, and H. Bueler Cell-Type-Specific Characteristics Modulate the Transduction Efficiency of Adeno-Associated Virus Type 2 and Restrain Infection of Endothelial Cells J. Virol., October 11, 2002; 76(22): 11530 - 11540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure Circ. Res., February 8, 2002; 90(2): 205 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Freedman Thrombin, Thrombomodulin, and Extracellular Signal-Regulated Kinases Regulating Cellular Proliferation Circ. Res., April 13, 2001; 88(7): 651 - 653. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, T. Kozai, B. van de Loo, H. Viswambharan, M. Lachat, M. I. Turina, T. Malinski, and T. F. Luscher HMG-CoA reductase inhibition improves endothelial cell function and inhibits smooth muscle cell proliferation in human saphenous veins J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1691 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. T. Ruschitzka, R. H. Wenger, T. Stallmach, T. Quaschning, C. de Wit, K. Wagner, R. Labugger, M. Kelm, G. Noll, T. Rulicke, et al. Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin PNAS, October 10, 2000; 97(21): 11609 - 11613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ruschitzka, U. Moehrlen, T. Quaschning, M. Lachat, G. Noll, S. Shaw, Z. Yang, D. Teupser, T. Subkowski, M. I. Turina, et al. Tissue Endothelin-Converting Enzyme Activity Correlates With Cardiovascular Risk Factors in Coronary Artery Disease Circulation, September 5, 2000; 102(10): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gruberg, G. Dangas, R. Mehran, M. K. Hong, R. Waksman, G. S. Mintz, K. M. Kent, A. D. Pichard, L. F. Satler, A. J. Lansky, et al. Percutaneous revascularization of the internal mammary artery graft: short- and long-term outcomes J. Am. Coll. Cardiol., March 15, 2000; 35(4): 944 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. Chardigny, K. Van der Perre, S. Simonet, J.-J. Descombes, J.-N. Fabiani, and T. J. Verbeuren Platelets and prostacyclin in arterial bypasses: implications for coronary artery surgery Ann. Thorac. Surg., February 1, 2000; 69(2): 513 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Rosenberg and W. C. Aird Vascular-Bed-Specific Hemostasis and Hypercoagulable States N. Engl. J. Med., May 20, 1999; 340(20): 1555 - 1564. [Full Text] [PDF]
|
|
|
|
|
|
J. G. Motwani and E. J. Topol Aortocoronary Saphenous Vein Graft Disease : Pathogenesis, Predisposition, and Prevention Circulation, March 10, 1998; 97(9): 916 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, B. S. Oemar, T. Carrel, B. Kipfer, F. Julmy, and T. F. Luscher Different Proliferative Properties of Smooth Muscle Cells of Human Arterial and Venous Bypass Vessels : Role of PDGF Receptors, Mitogen-Activated Protein Kinase, and Cyclin-Dependent Kinase Inhibitors Circulation, January 20, 1998; 97(2): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure Circ. Res., February 8, 2002; 90(2): 205 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Eto, C. Barandier, L. Rathgeb, T. Kozai, H. Joch, Z. Yang, and T. F. Luscher Thrombin Suppresses Endothelial Nitric Oxide Synthase and Upregulates Endothelin-Converting Enzyme-1 Expression by Distinct Pathways: Role of Rho/ROCK and Mitogen-Activated Protein Kinase Circ. Res., September 28, 2001; 89(7): 583 - 590. [Abstract] [Full Text] [PDF]
|
|