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

研究成果: Article同行評審

23 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)128-133
頁數6
期刊Thrombosis and Haemostasis
95
發行號1
DOIs
出版狀態Published - 2006 一月

All Science Journal Classification (ASJC) codes

  • 血液學

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