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DOI: 10.1055/s-0031-1284475
© Thieme Medical Publishers
Cyclic Strain Delays the Expression of Tissue Factor Induced by Thrombin in Human Umbilical Vein Endothelial Cells
Publikationsverlauf
Publikationsdatum:
19. Juli 2011 (online)

ABSTRACT
Most studies of tissue factor (TF) expression in endothelial cells (EC) are performed under stationary culture conditions. The purpose of this study was to determine the influence of mechanical stimuli such as cyclic strain (CS) on the expression of TF in EC exposed to thrombin (Thr). Human umbilical vein endothelial cells (HUVEC) were exposed to 4 U·mL−1 Thr in the presence or absence of 10% average CS at 60 cycles·min−1 and then TF expression was measured. TF messenger RNA (mRNA) expression peaked at 2 hours in HUVEC exposed to Thr, but at 4 hours in HUVEC exposed to both Thr + CS. TF expression was inhibited by p38 and extracellular signal-regulated protein kinase (ERK) inhibitors. For both Thr or Thr + CS stimuli, p38 and ERK activity peaked at 5 minutes (p < 0.05). Nuclear factor-kappa B levels remained high in the Thr group but not in the Thr + CS group, while Egr-1 levels were elevated in the Thr + CS group. We demonstrated CS-delayed, Thr-induced TF mRNA expression in HUVEC, which may be modulated by p38 and ERK inhibitors.
KEYWORDS
Hemodynamic forces - thrombin - endothelium - tissue factor - atherosclerosis
REFERENCES
- 1 von Eckardstein A. Risk factors for atherosclerotic vascular disease. Handb Exp Pharmacol. 2005; 170 71-105
- 2 DeBakey M E, Lawrie G M, Glaeser D H. Patterns of atherosclerosis and their surgical significance. Ann Surg. 1985; 201 (2) 115-131
- 3 Frangos S G, Gahtan V, Sumpio B. Localization of atherosclerosis: role of hemodynamics. Arch Surg. 1999; 134 (10) 1142-1149
- 4 Pradhan S, Sumpio B. Molecular and biological effects of hemodynamics on vascular cells. Front Biosci. 2004; 9 3276-3285
- 5 Kakisis J D, Liapis C D, Sumpio B E. Effects of cyclic strain on vascular cells. Endothelium. 2004; 11 (1) 17-28
- 6 Arditi M, Zhou J, Dorio R, Rong G W, Goyert S M, Kim K S. Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14. Infect Immun. 1993; 61 (8) 3149-3156
- 7 Liu Y, Pelekanakis K, Woolkalis M J. Thrombin and tumor necrosis factor alpha synergistically stimulate tissue factor expression in human endothelial cells: regulation through c-Fos and c-Jun. J Biol Chem. 2004; 279 (34) 36142-36147
- 8 Ueno H, Pradhan S, Schlessel D, Hirasawa H, Sumpio B E. Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1. Cardiovasc Toxicol. 2006; 6 (1) 39-50
- 9 Minami T, Sugiyama A, Wu S Q, Abid R, Kodama T, Aird W C. Thrombin and phenotypic modulation of the endothelium. Arterioscler Thromb Vasc Biol. 2004; 24 (1) 41-53
- 10 Camerer E, Kolstø A B, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res. 1996; 81 (1) 1-41
- 11 Crawley J, Lupu F, Westmuckett A D, Severs N J, Kakkar V V, Lupu C. Expression, localization, and activity of tissue factor pathway inhibitor in normal and atherosclerotic human vessels. Arterioscler Thromb Vasc Biol. 2000; 20 (5) 1362-1373
- 12 Day S M, Reeve J L, Pedersen B et al.. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood. 2005; 105 (1) 192-198
- 13 Westrick R J, Bodary P F, Xu Z, Shen Y C, Broze G J, Eitzman D T. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Circulation. 2001; 103 (25) 3044-3046
- 14 Azuma N, Duzgun S A, Ikeda M et al.. Endothelial cell response to different mechanical forces. J Vasc Surg. 2000; 32 (4) 789-794
- 15 Haga M, Chen A, Gortler D, Dardik A, Sumpio B E. Shear stress and cyclic strain may suppress apoptosis in endothelial cells by different pathways. Endothelium. 2003; 10 (3) 149-157
- 16 Zhang J J, Kelm R J, Biswas P, Kashgarian M, Madri J A. PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells. J Cell Physiol. 2007; 210 (2) 527-537
- 17 Pfaffl M W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29 (9) e45
- 18 Du W, Mills I, Sumpio B E. Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-kB, in endothelial cells: species and vascular bed diversity. J Biomech. 1995; 28 (12) 1485-1491
- 19 Maniatis T, Fritsch E F, Sambrook J. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1982
- 20 Li W, Sumpio B E. Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway. Am J Physiol Heart Circ Physiol. 2005; 288 (4) H1591-H1597
- 21 Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005; 29 (4) 169-175
- 22 Crossman D C, Carr D P, Tuddenham E G, Pearson J D, McVey J H. The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester. J Biol Chem. 1990; 265 (17) 9782-9787
- 23 Napoleone E, Di Santo A, Lorenzet R. Monocytes upregulate endothelial cell expression of tissue factor: a role for cell-cell contact and cross-talk. Blood. 1997; 89 (2) 541-549
- 24 Banfi C, Brioschi M, Barbieri S S et al.. Mitochondrial reactive oxygen species: a common pathway for PAR1- and PAR2-mediated tissue factor induction in human endothelial cells. J Thromb Haemost. 2009; 7 (1) 206-216
- 25 Mazzolai L, Silacci P, Bouzourene K, Daniel F, Brunner H, Hayoz D. Tissue factor activity is upregulated in human endothelial cells exposed to oscillatory shear stress. Thromb Haemost. 2002; 87 (6) 1062-1068
- 26 Lin M C, Almus-Jacobs F, Chen H H et al.. Shear stress induction of the tissue factor gene. J Clin Invest. 1997; 99 (4) 737-744
- 27 Silverman M D, Manolopoulos V G, Unsworth B R, Lelkes P I. Tissue factor expression is differentially modulated by cyclic mechanical strain in various human endothelial cells. Blood Coagul Fibrinolysis. 1996; 7 (3) 281-288
- 28 Steffel J, Lüscher T F, Tanner F C. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation. 2006; 113 (5) 722-731
- 29 Franke T F, Kaplan D R, Cantley L C. PI3K: downstream AKTion blocks apoptosis. Cell. 1997; 88 (4) 435-437
- 30 Vivanco I, Sawyers C L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002; 2 (7) 489-501
- 31 Gratton J P, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa W C. Akt down-regulation of p38 signaling provides a novel mechanism of vascular endothelial growth factor-mediated cytoprotection in endothelial cells. J Biol Chem. 2001; 276 (32) 30359-30365
- 32 Nishimura K, Li W, Hoshino Y et al.. Role of AKT in cyclic strain-induced endothelial cell proliferation and survival. Am J Physiol Cell Physiol. 2006; 290 (3) C812-C821
- 33 Hoshino Y, Nishimura K, Sumpio B E. Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain. J Cell Biochem. 2007; 100 (2) 515-526
- 34 Kito H, Chen E L, Wang X et al.. Role of mitogen-activated protein kinases in pulmonary endothelial cells exposed to cyclic strain. J Appl Physiol. 2000; 89 (6) 2391-2400
- 35 Kim J I, Cordova A C, Hirayama Y, Madri J A, Sumpio B E. Differential effects of shear stress and cyclic strain on Sp1 phosphorylation by protein kinase Czeta modulates membrane type 1-matrix metalloproteinase in endothelial cells. Endothelium. 2008; 15 (1) 33-42
- 36 Wung B S, Cheng J J, Chao Y J, Hsieh H J, Wang D L. Modulation of Ras/Raf/extracellular signal-regulated kinase pathway by reactive oxygen species is involved in cyclic strain-induced early growth response-1 gene expression in endothelial cells. Circ Res. 1999; 84 (7) 804-812
- 37 Cheng T H, Shih N L, Chen S Y et al.. Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in endothelial cells. J Mol Cell Cardiol. 2001; 33 (10) 1805-1814
- 38 Tai L K, Okuda M, Abe J, Yan C, Berk B C. Fluid shear stress activates proline-rich tyrosine kinase via reactive oxygen species-dependent pathway. Arterioscler Thromb Vasc Biol. 2002; 22 (11) 1790-1796
- 39 Han Z, Varadharaj S, Giedt R J, Zweier J L, Szeto H H, Alevriadou B R. Mitochondria-derived reactive oxygen species mediate heme oxygenase-1 expression in sheared endothelial cells. J Pharmacol Exp Ther. 2009; 329 (1) 94-101
- 40 Hawkins B J, Solt L A, Chowdhury I et al.. G protein-coupled receptor Ca2 + -linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. Mol Cell Biol. 2007; 27 (21) 7582-7593
- 41 Zieger M, Tausch S, Henklein P, Nowak G, Kaufmann R. A novel PAR-1-type thrombin receptor signaling pathway: cyclic AMP-independent activation of PKA in SNB-19 glioblastoma cells. Biochem Biophys Res Commun. 2001; 282 (4) 952-957
- 42 Sumpio B E, Yun S, Cordova A C et al.. MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells. J Biol Chem. 2005; 280 (12) 11185-11191
- 43 Tzima E, Irani-Tehrani M, Kiosses W B et al.. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature. 2005; 437 (7057) 426-431
Bauer E. SumpioM.D. Ph.D. F.A.C.S. F.I.C.A.
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