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 language | English |
|---|---|
| Pages (from-to) | 128-133 |
| Number of pages | 6 |
| Journal | Thrombosis and Haemostasis |
| Volume | 95 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2006 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Hematology
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Thrombomodulin plays an important role in arterial remodeling and neointima formation in mouse carotid ligation model. / Li, Yi Heng; Liu, Shu Liu; Shi, Guey Yueh; Tseng, Guan Hsiung; Liu, Ping Yen; Wu, Hua Lin.
In: Thrombosis and Haemostasis, Vol. 95, No. 1, 01.01.2006, p. 128-133.Research output: Contribution to journal › Article
TY - JOUR
T1 - Thrombomodulin plays an important role in arterial remodeling and neointima formation in mouse carotid ligation model
AU - Li, Yi Heng
AU - Liu, Shu Liu
AU - Shi, Guey Yueh
AU - Tseng, Guan Hsiung
AU - Liu, Ping Yen
AU - Wu, Hua Lin
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
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U2 - 10.1160/TH05-06-0415
DO - 10.1160/TH05-06-0415
M3 - Article
C2 - 16543971
AN - SCOPUS:33645536018
VL - 95
SP - 128
EP - 133
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 1
ER -