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

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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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 of TM 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. Recombinant TMD123 and saline was administered immediately before and after carotid Iigation. 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 in TM 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.

Original languageEnglish
Pages (from-to)128-133
Number of pages6
JournalThrombosis and Haemostasis
Volume95
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

All Science Journal Classification (ASJC) codes

  • Hematology

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