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

Hong-Ya Xin; De-Jian Jiang; Su-Jie Jia; Kui Song; Guang-Ping Wang; Yuan-Jian Li; Fang-Ping Chen

doi:10.1160/TH06-11-0656

Thrombosis and Haemostasis, Inhaltsverzeichnis

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^*

¹Department of Hematology, Xiangya Hospital of Central South University, Changsha, China

,

De-Jian Jiang^*

²Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China

,

Su-Jie Jia

²Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China

,

Kui Song

¹Department of Hematology, Xiangya Hospital of Central South University, Changsha, China

,

Guang-Ping Wang

¹Department of Hematology, Xiangya Hospital of Central South University, Changsha, China

,

Yuan-Jian Li

²Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China

,

Fang-Ping Chen

¹Department of Hematology, Xiangya Hospital of Central South University, Changsha, China

› Institutsangaben

Abstract

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

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Referenzen

References
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