Thrombomodulin plays an important role in arterial remodeling and neointima formation in mouse carotid ligation model

Yi-Heng Li; Shu-Lin Liu; Guey-Yueh Shi; Guan-Hsiung Tseng; Ping-Yen Liu; Hua-Lin Wu

doi:10.1160/TH05-06-0415

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 128-133
DOI: 10.1160/TH05-06-0415

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Thrombomodulin plays an important role in arterial remodeling and neointima formation in mouse carotid ligation model

Yi-Heng Li

¹Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Shu-Lin Liu

²Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Guey-Yueh Shi

²Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Guan-Hsiung Tseng

²Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Ping-Yen Liu

¹Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

Hua-Lin Wu

²Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

› Author Affiliations

Abstract

Summary

Thrombomodulin (TM) is a cell membrane-bound glycoprotein that functions as a thrombin cofactor in the activation of protein C. Its protein structure includes a N-terminal lectin-like domain (D1), 6 epidermal growth factor repeats (D2), a serine-threonine-rich region (D3), a transmembrane domain (D4) and a short cytoplasmic tail (D5). Recent studies have demonstrated the direct effect ofTM on cellular proliferation, adhesion and inflammation. In the study, we investigated the role of TM in vascular remodeling and neointima formation in a mouse carotid ligation model. TM expressions on the endothelium, neointima and media were examined in the ligated carotid artery by immunohistochemistry and quantitative real-time reverse transcription PCR. Endothelial TM expression decreased after ligation and appeared later in the media and neointima, which is quite similar to the appearance of TM in the human atherosclerotic process. Recombinant TMD123 was prepared. It was effective for thrombin-dependent protein C activation and the inhibition of leukocyte adhesion to the vessel wall after carotid ligation. RecombinantTMD123 and saline was administered immediately before and after carotid ligation. The TM-treated arteries demonstrated significantly less arterial dilatation (30279±12605 vs 73789±15073 µm², p<0.05) in response to less neointima formation (14179±6538 vs 42227±8754 µm², p<0.05) at 4 weeks after ligation. Our data indicated that there was a compensatory increase inTM expression in the media and neointima in relation to the reduced endothelial TM after carotid ligation. Early recombinant TM treatment in mice undergoing carotid ligation altered vascular remodeling and decreased the severity of neointima formation.

Keywords

Thrombomodulin - atherosclerosis - neointima

Full Text

References

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