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
› Author Affiliations
Financial support: This work was supported in part by the National Postdoctoral Science Foundation (20060390262) and the Provincial Natural Science Foundation of Hunan (06jj3012), China.
Further Information

Publication History

Received 21 November 2006

Accepted after resubmission 06 March 2007

Publication Date:
24 November 2017 (online)

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.

* These authors contributed equally to this work.