Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:41-53
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000099880.09014.7D
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000099880.09014.7D
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Brief Reviews |
Thrombin and Phenotypic Modulation of the Endothelium
From the Research Center for Advanced Science and Technology (T.M., A.S., T.K.), University of Tokyo, Tokyo, Japan, and the Division of Molecular and Vascular Medicine (S.W., R.A., W.C.A.), Beth Israel–Deaconess Medical Center/Harvard Medical School, Boston, Mass.
Correspondence to William C. Aird, Beth Israel Deaconess Medical Center, RW-663, Boston, MA 02215. E-mail waird{at}bidmc.harvard.edu
Thrombin signaling in the endothelium is linked to multiple phenotypic changes, including alterations in permeability, vasomotor tone, and leukocyte trafficking. The thrombin signal is transduced, at least in part, at the level of gene transcription. In this review, we focus on the role of thrombin signaling and transcriptional networks in mediating downstream gene expression and endothelial phenotype. In addition, we report the results of DNA microarrays in control and thrombin-treated endothelial cells. We conclude that (1) thrombin induces the upregulation and downregulation of multiple genes in the endothelium, (2) thrombin-mediated gene expression involves a multitude of transcription factors, and (3) future breakthroughs in the field will depend on a better understanding of the spatial and temporal dynamics of these transcriptional networks.
Key Words: thrombin • transcription • DNA microarrays • endothelial cells
This article has been cited by other articles:
 |
|
 |
|
  M. Popovic, Y. Laumonnier, L. Burysek, T. Syrovets, and T. Simmet Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration J. Leukoc. Biol., July 1, 2008; 84(1): 215 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Bijli, F. Fazal, M. Minhajuddin, and A. Rahman Activation of Syk by Protein Kinase C-{delta} Regulates Thrombin-induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Tyrosine Phosphorylation of RelA/p65 J. Biol. Chem., May 23, 2008; 283(21): 14674 - 14684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Singleton, L. Moreno-Vinasco, S. Sammani, S. L. Wanderling, J. Moss, and J. G. N. Garcia Attenuation of Vascular Permeability by Methylnaltrexone: Role of mOP-R and S1P3 Transactivation Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 222 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Arciniegas, M. G. Frid, I. S. Douglas, and K. R. Stenmark Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L1 - L8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ahamed, F. Niessen, T. Kurokawa, Y. K. Lee, G. Bhattacharjee, J. H. Morrissey, and W. Ruf Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia Blood, June 15, 2007; 109(12): 5251 - 5259. [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]
|
|
|
|
 |
|
 E. D. Motley, K. Eguchi, M. M. Patterson, P. D. Palmer, H. Suzuki, and S. Eguchi Mechanism of Endothelial Nitric Oxide Synthase Phosphorylation and Activation by Thrombin Hypertension, March 1, 2007; 49(3): 577 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Touyz Regulation of Endothelial Nitric Oxide Synthase by Thrombin Hypertension, March 1, 2007; 49(3): 429 - 431. [Full Text] [PDF]
|
|
|
|
|
|
F. Fazal, M. Minhajuddin, K. M. Bijli, J. L. McGrath, and A. Rahman Evidence for Actin Cytoskeleton-dependent and -independent Pathways for RelA/p65 Nuclear Translocation in Endothelial Cells J. Biol. Chem., February 9, 2007; 282(6): 3940 - 3950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Bijli, M. Minhajuddin, F. Fazal, M. A. O'Reilly, L. C. Platanias, and A. Rahman c-Src interacts with and phosphorylates RelA/p65 to promote thrombin-induced ICAM-1 expression in endothelial cells Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L396 - L404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hirano The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 27 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Inoue, M. Kobayashi, K. Yano, M. Miura, A. Izumi, C. Mataki, T. Doi, T. Hamakubo, P. C. Reid, D. A. Hume, et al. Histone Deacetylase Inhibitor Reduces Monocyte Adhesion to Endothelium Through the Suppression of Vascular Cell Adhesion Molecule-1 Expression Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2652 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sapet, S. Simoncini, B. Loriod, D. Puthier, J. Sampol, C. Nguyen, F. Dignat-George, and F. Anfosso Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2 Blood, September 15, 2006; 108(6): 1868 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Leger, L. Covic, and A. Kuliopulos Protease-Activated Receptors in Cardiovascular Diseases Circulation, September 5, 2006; 114(10): 1070 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Stahmann, A. Woods, D. Carling, and R. Heller Thrombin Activates AMP-Activated Protein Kinase in Endothelial Cells via a Pathway Involving Ca2+/Calmodulin-Dependent Protein Kinase Kinase {beta}. Mol. Cell. Biol., August 1, 2006; 26(16): 5933 - 5945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minami, M. Miura, W. C. Aird, and T. Kodama Thrombin-induced Autoinhibitory Factor, Down Syndrome Critical Region-1, Attenuates NFAT-dependent Vascular Cell Adhesion Molecule-1 Expression and Inflammation in the Endothelium J. Biol. Chem., July 21, 2006; 281(29): 20503 - 20520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Lin, A. Hamik, R. Jain, A. Kumar, and M. K. Jain Kruppel-Like Factor 2 Inhibits Protease Activated Receptor-1 Expression and Thrombin-Mediated Endothelial Activation Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1185 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Syeda, J. Grosjean, R. A. Houliston, R. J. Keogh, T. D. Carter, E. Paleolog, and C. P. D. Wheeler-Jones Cyclooxygenase-2 Induction and Prostacyclin Release by Protease-activated Receptors in Endothelial Cells Require Cooperation between Mitogen-activated Protein Kinase and NF-{kappa}B Pathways J. Biol. Chem., April 28, 2006; 281(17): 11792 - 11804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Lidington, R. Steinberg, A. R. Kinderlerer, R. C. Landis, M. Ohba, A. Samarel, D. O. Haskard, and J. C. Mason A role for proteinase-activated receptor 2 and PKC-{epsilon} in thrombin-mediated induction of decay-accelerating factor on human endothelial cells Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1437 - C1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. David-Dufilho, E. M.-V. Brussel, G. Topal, L. Walch, A. Brunet, and F. Rendu Endothelial Thrombomodulin Induces Ca2+ Signals and Nitric Oxide Synthesis through Epidermal Growth Factor Receptor Kinase and Calmodulin Kinase II J. Biol. Chem., October 28, 2005; 280(43): 35999 - 36006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zhang, X. Liu, J. G. Cogan, M. D. Fuerst, J. A. Polikandriotis, R. J. Kelm Jr., and A. R. Strauch YB-1 Coordinates Vascular Smooth Muscle {alpha}-Actin Gene Activation by Transforming Growth Factor {beta}1 and Thrombin during Differentiation of Human Pulmonary Myofibroblasts Mol. Biol. Cell, October 1, 2005; 16(10): 4931 - 4940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Q. Wu and W. C. Aird Thrombin, TNF-{alpha}, and LPS exert overlapping but nonidentical effects on gene expression in endothelial cells and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H873 - H885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Feistritzer and M. Riewald Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation Blood, April 15, 2005; 105(8): 3178 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Ray, D. A. Morrow, C. M. Gibson, S. Murphy, E. M. Antman, E. Braunwald, and for the ENTIRE-TIMI 23 Study Group Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRE-TIMI 23 substudy Eur. Heart J., March 1, 2005; 26(5): 440 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Undas, K. E. Brummel-Ziedins, and K. G. Mann Statins and Blood Coagulation Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Manalo, A. Rowan, T. Lavoie, L. Natarajan, B. D. Kelly, S. Q. Ye, J. G. N. Garcia, and G. L. Semenza Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1 Blood, January 15, 2005; 105(2): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Anwar, F. Fazal, A. B. Malik, and A. Rahman RhoA/Rho-Associated Kinase Pathway Selectively Regulates Thrombin-Induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Activation of I{kappa}B Kinase {beta} and Phosphorylation of RelA/p65 J. Immunol., December 1, 2004; 173(11): 6965 - 6972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minami, K. Horiuchi, M. Miura, Md. R. Abid, W. Takabe, N. Noguchi, T. Kohro, X. Ge, H. Aburatani, T. Hamakubo, et al. Vascular Endothelial Growth Factor- and Thrombin-induced Termination Factor, Down Syndrome Critical Region-1, Attenuates Endothelial Cell Proliferation and Angiogenesis J. Biol. Chem., November 26, 2004; 279(48): 50537 - 50554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Chandrasekharan, L. Yang, A. Walters, P. Howe, and P. E. DiCorleto Role of CL-100, a Dual Specificity Phosphatase, in Thrombin-induced Endothelial Cell Activation J. Biol. Chem., November 5, 2004; 279(45): 46678 - 46685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. de Wouwer, D. Collen, and E. M. Conway Thrombomodulin-Protein C-EPCR System: Integrated to Regulate Coagulation and Inflammation Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1374 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pal, M. J. Nemeth, D. Bodine, J. L. Miller, J. Svaren, S. L. Thein, P. J. Lowry, and E. H. Bresnick Neurokinin-B Transcription in Erythroid Cells: DIRECT ACTIVATION BY THE HEMATOPOIETIC TRANSCRIPTION FACTOR GATA-1 J. Biol. Chem., July 23, 2004; 279(30): 31348 - 31356. [Abstract] [Full Text] [PDF]
|
|