PDF herunterladen
Thromb Haemost 2007; 97(05): 830-838
DOI: 10.1160/TH06-11-0656
Endothelium and Vascular Development
Schattauer GmbH

Regulation by DDAH/ADMA pathway of lipopolysaccharideinduced tissue factor expression in endothelial cells

Hong-Ya Xin   *
1   Department of Hematology, Xiangya Hospital of Central South University, Changsha, China
,
De-Jian Jiang   *
2   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Su-Jie Jia
2   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Kui Song
1   Department of Hematology, Xiangya Hospital of Central South University, Changsha, China
,
Guang-Ping Wang
1   Department of Hematology, Xiangya Hospital of Central South University, Changsha, China
,
Yuan-Jian Li
2   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Fang-Ping Chen
1   Department of Hematology, Xiangya Hospital of Central South University, Changsha, China
› InstitutsangabenFinancial support: This work was supported in part by the National Postdoctoral Science Foundation (20060390262) and the Provincial Natural Science Foundation of Hunan (06jj3012), China.
Weitere Informationen

Publikationsverlauf

Received 21. November 2006

Accepted after resubmission 06. März 2007

Publikationsdatum:
24. November 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

Previous studies have shown the regulatory effect of nitric oxide (NO) on endotoxin-induced tissue factor (TF) in endothelial cells. Asymmetric dimethylarginine (ADMA), a major endogenous NO synthase (NOS) inhibitor, could inhibit NO production in vivo and in vitro. ADMA and its major hydrolase dimethylarginine dimethylaminohydrolase (DDAH) have recently been thought of as a novel regulatory system of endogenous NO production. The aim of the present study was to determine whether the DDAH/ADMA pathway is involved in the effect of lipopolysaccharide (LPS) on TF expression in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were treated with LPS (1 µ g/ml) to induce TF expression. Exogenous ADMA significantly enhanced the increase in both TF mRNA level and activity induced by LPS, whereas L-arginine, the NOS substrate, markedly attenuated the LPS-induced TF increment. LPS markedly increased the level of ADMA in cultured medium and decreased DDAH activity in endothelial cells, and overexpression of DDAH2 could significantly suppress LPS-induced TF increment in endothelial cells. LPS could increase intracellular reactive oxygen species (ROS) production and activate nuclear factor-κ B, which were enhanced by exogenous ADMA and attenuated by either L-arginine or overexpression of DDAH2. Therefore, our present results for the first time suggest that the DDAH/ADMA pathway can regulate LPS-inducedTF expression via ROS-nuclear factor- κ B-dependent pathway in endothelial cells.

Keywords

Asymmetric dimethylarginine - dimethylarginine dimethylaminohydrolase - endothelial cells - lipopolysaccharide - nuclear factor-κ B - tissue factor

* These authors contributed equally to this work.


 

  • References

  • 1 ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000; 28 (Suppl. 09) (Suppl) S9-11.
    CrossrefPubMedGoogle Scholar
  • 2 Levi M, ten Cate H, Bauer KA. et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-120.
    CrossrefPubMedGoogle Scholar
  • 3 Taylor Jr FB, Chang A, Ruf W. et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-134.
    PubMedGoogle Scholar
  • 4 Warr TA, Rao LV, Rapaport SI. Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: Effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. Blood 1990; 75: 1481-1489.
    PubMedGoogle Scholar
  • 5 Crossman DC, Carr DP, Tuddenham EG. et al. The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester. J Biol Chem 1990; 265: 9782-9787.
    PubMedGoogle Scholar
  • 6 Steffel J, Hermann M, Greutert H. et al. Celecoxib decreases endothelial tissue factor expression through inhibition of c-Jun terminal NH2 kinase phosphorylation. Circulation 2005; 111: 1685-1689.
    CrossrefPubMedGoogle Scholar
  • 7 Walford G, Loscalzo J. Nitric oxide in vascular biology. J Thromb Haemost 2003; 01: 2112-2118.
    CrossrefPubMedGoogle Scholar
  • 8 Thiemermann C. Nitric oxide and septic shock. Gen Pharmacol 1997; 29: 159-166.
    CrossrefPubMedGoogle Scholar
  • 9 Yang Y, Loscalzo J. Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide. Circulation 2000; 101: 2144-2148.
    CrossrefPubMedGoogle Scholar
  • 10 Perez-Ruiz A, Montes R, Velasco F. et al. Regulation by nitric oxide of endotoxin-induced tissue factor and plasminogen activator inhibitor-1 in endothelial cells. Thromb Haemost 2002; 88: 1060-1065.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 11 Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovasc Res 1999; 43: 542-548.
    CrossrefPubMedGoogle Scholar
  • 12 Dayoub H, Achan V, Adimoolam S. et al. Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiological evidence. Circulation 2003; 108: 3042-3047.
    CrossrefPubMedGoogle Scholar
  • 13 MacAllister RJ, Parry H, Kimoto M. et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1533-1540.
    CrossrefPubMedGoogle Scholar
  • 14 Leiper J, Murray-Rust J, McDonald N. et al. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci USA 2002; 99: 13527-13532.
    CrossrefPubMedGoogle Scholar
  • 15 Jiang DJ, Jia SJ, Yan J. et al. Involvement of DDAH/ ADMA/NOS pathway in nicotine-induced endothelial dysfunction. Biochem Biophys Res Commun 2006; 349: 683-693.
    CrossrefPubMedGoogle Scholar
  • 16 Ito A, Tsao PS, Adimoolam S. et al. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99: 3092-3095.
    CrossrefPubMedGoogle Scholar
  • 17 Chen BM, Xia LW, Zhao RQ. Determination of NG, NG-dimethylarginine in human plasma by highperformance liquid chromatography. J Chromatogr B Biomed Appl 1997; 692: 467-471.
    CrossrefPubMedGoogle Scholar
  • 18 Lin KY, Ito A, Asagami T, Tsao PS. et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106: 987-992.
    CrossrefPubMedGoogle Scholar
  • 19 Hasegawa K, Wakino S, Tanaka T. et al. Dimethylarginine dimethylaminohydrolase 2 increases vasc endothelial growth factor expression through Sp1 transcription factor in endothelial cells. Arterioscler Thromb Vasc Biol 2006; 26: 1488-1494.
    CrossrefPubMedGoogle Scholar
  • 20 Simeonidis S, Castagliuolo I, Pan A. et al. Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-kappa B site on its promoter. Proc Natl Acad Sci USA 2003; 100: 2957-2962.
    CrossrefPubMedGoogle Scholar
  • 21 Harbrecht BG, Billiar TR, Stadler J. et al. Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J Leukoc Biol 1992; 52: 390-394.
    CrossrefPubMedGoogle Scholar
  • 22 Jourdain M, Tournoys A, Leroy X. et al. Effects of Nomega-nitro-Larginine methyl ester on the endotoxin- induced disseminated intravascular coagulation in porcine septic shock. Crit Care Med 1997; 25: 452-459.
    CrossrefPubMedGoogle Scholar
  • 23 Shultz PJ, Raij L. Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. J Clin Invest 1992; 90: 1718-1725.
    CrossrefPubMedGoogle Scholar
  • 24 Westberg G, Shultz PJ, Raij L. Exogenous nitric oxide prevents endotoxin induced glomerular thrombosis in rats. Kidney Int 1994; 46: 711-716.
    CrossrefPubMedGoogle Scholar
  • 25 Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 2004; 24: 1023-1030.
    CrossrefPubMedGoogle Scholar
  • 26 Leiper JM, Santa Maria J, Chubb A. et al. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 1999; 343: 209-214.
    CrossrefPubMedGoogle Scholar
  • 27 Jiang DJ, Jiang JL, Tan GS. et al. Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine. Naunyn Schmiedebergs Arch Pharmacol 2003; 367: 600-606.
    CrossrefPubMedGoogle Scholar
  • 28 Maas R. Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA). Vasc Med 2005; 10 (Suppl. 01) (Suppl) S49-57.
    CrossrefPubMedGoogle Scholar
  • 29 Niiya Y, Abumiya T, Shichinohe H. et al. Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation is associated with intracellular reactive oxygen species. Brain Res 2006; 1108: 179-187.
    CrossrefPubMedGoogle Scholar
  • 30 Jacobi J, Kristal B, Chezar J. et al. Exogenous superoxide mediates pro-oxidative, proinflammatory, and procoagulatory changes in primary endothelial cell cultures. Free Radic Biol Med 2005; 39: 1238-1248.
    CrossrefPubMedGoogle Scholar
  • 31 Chan EL, Murphy JT. Reactive oxygen species mediate endotoxin-induced human dermal endothelial NF-kappaB activation. J Surg Res 2003; 111: 120-126.
    CrossrefPubMedGoogle Scholar
  • 32 Böger RH, Bode-Boger SM, Tsao PS. et al. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 2000; 36: 2287-2295.
    CrossrefPubMedGoogle Scholar
  • 33 Parry GC, Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol 1995; 15: 612-621.
    CrossrefPubMedGoogle Scholar
  • 34 Orthner CL, Rodgers GM, Fitzgerald LA. Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: evidence implicating nuclear factor-kappa B in TF induction by diverse agonists. Blood 1995; 86: 436-443.
    PubMedGoogle Scholar
  • 35 Mittermayer F, Namiranian K, Pleiner J. et al. Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans. Clin Sci (Lond) 2004; 106: 577-581.
    CrossrefPubMedGoogle Scholar
  • 36 Nijveldt RJ, Siroen MP, Teerlink T. et al. Gut and liver handling of asymmetric and symmetric dimethylarginine in the rat under basal conditions and during en-.
    PubMedGoogle Scholar