Expression of Protein S in the Murine Heart and Cultured Mouse Cardiomyocytes Is Down-regulated by Cytokines

Takayoshi Shimokawa; Koji Yamamoto; Eriko Yamafuji; Tetsuhito Kojima; Hidehiko Saito

doi:10.1055/s-0037-1616096

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(02): 623-629
DOI: 10.1055/s-0037-1616096

Review Article

Schattauer GmbH

Expression of Protein S in the Murine Heart and Cultured Mouse Cardiomyocytes Is Down-regulated by Cytokines

Takayoshi Shimokawa

¹First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Koji Yamamoto

¹First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

²Aichi Blood Disease Research Foundation, Nagoya, Japan

,

Eriko Yamafuji

¹First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Tetsuhito Kojima

³Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan

,

Hidehiko Saito

¹First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

› Author Affiliations

Abstract

Summary

Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependent anticoagulant protein and is known to be produced extrahepatically. In the present study, the concentration of PS mRNA was determined tissue by tissue in the mouse, and it was high in lung, adrenal and heart as well as in liver. We further investigated the effects of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) on the PS mRNA expression in murine tissues in vivo. Although LPS and TNF-α significantly decreased the expression level of PS mRNA in all tissues examined (e.g., lung, liver, heart, and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell line, and again, treatment with IL-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regional anticoagulant potential in heart, and suggest that the decreased PS expression by cytokines may result in an increase in the systemic and/or regional prothrombotic potential under inflammatory conditions.

Keywords

Anticoagulant - interleukin-1 - tumor necrosis factor-α - cardiomyocyte - gene regulation

Full Text

References

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