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Thromb Haemost 2001; 85(06): 1104-1110
DOI: 10.1055/s-0037-1615970
Review Article
Schattauer GmbH

Thrombin-induced MCP-1 Expression Involves Activation of the p22phox-containing NADPH Oxidase in Human Vascular Smooth Muscle Cells

R. P. Brandes
,
C. Viedt
1   Innere Medizin III, Universität Heidelberg, Germany
,
K. Nguyen
,
S. Beer
,
J. Kreuzer
1   Innere Medizin III, Universität Heidelberg, Germany
,
R. Busse
,
A. Görlach
› Author Affiliations
Further Information

Publication History

Received 24 July 2000

Accepted after resubmission 13 February 2000

Publication Date:
12 December 2017 (online)

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Summary

Activation of vascular smooth muscle cells (VMSC) by thrombin induces the expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1). We investigated in cultured human and rat VSMC whether reactive oxygen species (ROS) derived from the vascular NADPH oxidase contribute to this effect. Exposure of cultured VSMC to thrombin rapidly increased ROS formation, phosphorylation of p38 MAP kinase as well as the expression of MCP-1. Specific inhibition of the p22phox subunit of the vascular NADPH oxidase using either p22phox neutralizing antibody or p22phox antisense oligonucleotides attenuated thrombin-induced ROS generation. Furthermore, thrombininduced p38 MAP kinase activation as well as MCP-1 expression were impaired by antioxidants as well as by p22phox antisense oligonucleotides. Inhibition of p38 MAP kinase diminished the thrombin-induced expression of MCP-1. Conclusion: Thrombin, by activating a p22phoxcontaining NADPH oxidase, elicits ROS generation and activation of p38 MAP kinase in VSMC. The subsequent induction of MCP-1 expression highligts the crucial role of the p22phox-containing NADPH oxidase in thrombin-induced signal transduction in VSMC.

Key words

Oxidative stress - thrombin - NADPH oxidase - p22phox - MCP-1
 

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