This Article Full Text Full Text (PDF) All Versions of this Article: 23/4/681    most recent 01.ATV.0000065194.00822.C7v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Ishibashi, T. Articles by Maruyama, Y. Search for Related Content PubMed PubMed Citation Articles by Ishibashi, T. Articles by Maruyama, Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Cell signalling/signal transduction Anticoagulant mechanisms Coagulation and fibronolysis

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:681.)
© 2003 American Heart Association, Inc.

Thrombosis

Integral Role of RhoA Activation in Monocyte Adhesion–Triggered Tissue Factor Expression in Endothelial Cells

Toshiyuki Ishibashi; Takayuki Sakamoto; Hiroshi Ohkawara; Kenji Nagata; Koichi Sugimoto; Sotaro Sakurada; Naotoshi Sugimoto; Atai Watanabe; Keiko Yokoyama; Nobuo Sakamoto; Masahiko Kurabayashi; Yoh Takuwa; Yukio Maruyama

From the First Department of Internal Medicine (T.I., T.S., H.O., K.N., K.S., K.Y., Y.M.), Fukushima Medical University, Fukushima; the Department of Physiology (S.S., N.S., N.S., Y.T.), Kanazawa University School of Medicine, Kanazawa; and the Second Department of Internal Medicine (A.W., M.K.), Gunma University School of Medicine, Maebashi, Japan.

Correspondence to Yukio Maruyama, MD, First Department of Internal Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan. E-mail maruyama{at}fmu.ac.jp

Objective— The role of Rho activation in the regulation of tissue factor (TF) is not clear. This study was undertaken to investigate this in endothelial cells induced by monocyte adhesion.

Methods and Results— Isolated human peripheral blood monocytes were added to cultured human coronary endothelial cells. Monocyte adhesion to endothelial cells increased the levels of TF antigen in the endothelial cells. The results of transient transfection of the human TF promoter/luciferase gene into endothelial cells indicated that the increase in endothelial expression of the TF gene caused by monocyte adhesion occurred at the transcriptional level. The upregulation of TF was inhibited by statins, and the suppressive effect of statins was reversed by geranylgeranylpyrophosphate. Monocyte adhesion rapidly upregulated the membrane translocation and GTP/GDP exchange of RhoA, but not of Cdc42 or Rac, in endothelial cells. Rho inhibition by C3 exoenzyme or adenovirus-mediated expression of N19RhoA prevented the endothelial upregulation of TF caused by monocyte adhesion, and this was mimicked by Rho-kinase inhibitors. Moreover, monocyte adhesion increased the phosphorylation of nuclear factor-B p65 in endothelial cells, and this was prevented by statins and Rho inhibition.

Conclusions— Our study shows that RhoA activation plays an integral role in TF expression in endothelial cells.

Key Words: endothelial cell • monocyte adhesion • Rho • tissue factor • statin

This article has been cited by other articles:

				K. Sugimoto, T. Ishibashi, T. Sawamura, N. Inoue, M. Kamioka, H. Uekita, H. Ohkawara, T. Sakamoto, N. Sakamoto, Y. Okamoto, et al. LOX-1-MT1-MMP axis is crucial for RhoA and Rac1 activation induced by oxidized low-density lipoprotein in endothelial cells Cardiovasc Res, October 1, 2009; 84(1): 127 - 136. [Abstract] [Full Text] [PDF]

				S. Camino-Lopez, V. Llorente-Cortes, J. Sendra, and L. Badimon Tissue factor induction by aggregated LDL depends on LDL receptor-related protein expression (LRP1) and Rho A translocation in human vascular smooth muscle cells Cardiovasc Res, January 1, 2007; 73(1): 208 - 216. [Abstract] [Full Text] [PDF]

				T. Sakamoto, T. Ishibashi, N. Sakamoto, K. Sugimoto, K. Egashira, H. Ohkawara, K. Nagata, K. Yokoyama, M. Kamioka, T. Ichiki, et al. Endogenous NO Blockade Enhances Tissue Factor Expression via Increased Ca2+ Influx Through MCP-1 in Endothelial Cells by Monocyte Adhesion Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 2005 - 2011. [Abstract] [Full Text] [PDF]

				H. Ohkawara, T. Ishibashi, T. Sakamoto, K. Sugimoto, K. Nagata, K. Yokoyama, N. Sakamoto, M. Kamioka, I. Matsuoka, S. Fukuhara, et al. Thrombin-induced Rapid Geranylgeranylation of RhoA as an Essential Process for RhoA Activation in Endothelial Cells J. Biol. Chem., March 18, 2005; 280(11): 10182 - 10188. [Abstract] [Full Text] [PDF]

				A. Solovey, R. Kollander, A. Shet, L. C. Milbauer, S. Choong, A. Panoskaltsis-Mortari, B. R. Blazar, R. J. Kelm Jr, and R. P. Hebbel Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin Blood, August 1, 2004; 104(3): 840 - 846. [Abstract] [Full Text] [PDF]

				H. Viswambharan, X.-F. Ming, S. Zhu, A. Hubsch, P. Lerch, G. Vergeres, S. Rusconi, and Z. Yang Reconstituted High-Density Lipoprotein Inhibits Thrombin-Induced Endothelial Tissue Factor Expression Through Inhibition of RhoA and Stimulation of Phosphatidylinositol 3-Kinase but not Akt/Endothelial Nitric Oxide Synthase Circ. Res., April 16, 2004; 94(7): 918 - 925. [Abstract] [Full Text] [PDF]

				M. M. Monick, L. S. Powers, N. S. Butler, and G. W. Hunninghake Inhibition of Rho Family GTPases Results in Increased TNF-{alpha} Production After Lipopolysaccharide Exposure J. Immunol., September 1, 2003; 171(5): 2625 - 2630. [Abstract] [Full Text] [PDF]