Soluble thrombomodulin is a paracrine anti-apoptotic factor for vascular endothelial protection

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Abstract

Background Thrombomodulin (TM) is an endothelial cell (EC) membrane-bound anticoagulant protein that has novel direct cellular effects. TM is shed from EC and becomes soluble form (sTM) in plasma. Higher sTM levels in healthy subjects are associated with lower cardiovascular risk, suggesting that sTM possesses a protective role. The purpose of the study was to evaluate the effect of sTM on vascular endothelium. Methods and results Apoptosis of cultured ECs was induced via serum starvation. EC-bound TM was released into the medium after serum starvation. The medium conditioned by serum-starved EC decreased apoptosis in another set of cultured EC. Direct treatment with sTM reduced EC apoptosis and decreased pro-apoptotic protein expression. TM knockdown in EC exacerbated the rate of serum starvation-induced apoptosis. Treatment of sTM activated the phosphatidylinositol 3-kinase (PI3 kinase)-protein kinase B/Akt survival pathway and suppressed the death pathway, c-Jun N-terminal kinase. We found that sTM also increased growth and reduced apoptosis of endothelial progenitor cells. Conclusions EC-bound TM is released during stress-induced EC damage and becomes sTM, a paracrine factor that exerts anti-apoptotic activity. Our data indicate that sTM is not only an endothelial injury biomarker but also has cytoprotective effects on vascular endothelium.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalInternational Journal of Cardiology
Volume172
Issue number2
DOIs
Publication statusPublished - 2014 Mar 15

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Thrombomodulin
Endothelial Cells
Apoptosis
Starvation
Vascular Endothelium
Serum
Phosphatidylinositol 3-Kinase
vascular factor
Proto-Oncogene Proteins c-akt
Apoptosis Regulatory Proteins
JNK Mitogen-Activated Protein Kinases
Conditioned Culture Medium
Anticoagulants
Cultured Cells
Healthy Volunteers
Biomarkers
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{1461fb09419a4aabba2e211c49485c04,
title = "Soluble thrombomodulin is a paracrine anti-apoptotic factor for vascular endothelial protection",
abstract = "Background Thrombomodulin (TM) is an endothelial cell (EC) membrane-bound anticoagulant protein that has novel direct cellular effects. TM is shed from EC and becomes soluble form (sTM) in plasma. Higher sTM levels in healthy subjects are associated with lower cardiovascular risk, suggesting that sTM possesses a protective role. The purpose of the study was to evaluate the effect of sTM on vascular endothelium. Methods and results Apoptosis of cultured ECs was induced via serum starvation. EC-bound TM was released into the medium after serum starvation. The medium conditioned by serum-starved EC decreased apoptosis in another set of cultured EC. Direct treatment with sTM reduced EC apoptosis and decreased pro-apoptotic protein expression. TM knockdown in EC exacerbated the rate of serum starvation-induced apoptosis. Treatment of sTM activated the phosphatidylinositol 3-kinase (PI3 kinase)-protein kinase B/Akt survival pathway and suppressed the death pathway, c-Jun N-terminal kinase. We found that sTM also increased growth and reduced apoptosis of endothelial progenitor cells. Conclusions EC-bound TM is released during stress-induced EC damage and becomes sTM, a paracrine factor that exerts anti-apoptotic activity. Our data indicate that sTM is not only an endothelial injury biomarker but also has cytoprotective effects on vascular endothelium.",
author = "Chao, {Ting Hsing} and Tsai, {Wei Chuan} and Chen, {Ju Yi} and Liu, {Ping Yen} and Chung, {Hsing Chun} and Tseng, {Shi Ya} and Kuo, {Cheng Hsiang} and Shi, {Guey Yueh} and Wu, {Hua Lin} and Li, {Yi Heng}",
year = "2014",
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doi = "10.1016/j.ijcard.2014.01.009",
language = "English",
volume = "172",
pages = "340--349",
journal = "International Journal of Cardiology",
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T1 - Soluble thrombomodulin is a paracrine anti-apoptotic factor for vascular endothelial protection

AU - Chao, Ting Hsing

AU - Tsai, Wei Chuan

AU - Chen, Ju Yi

AU - Liu, Ping Yen

AU - Chung, Hsing Chun

AU - Tseng, Shi Ya

AU - Kuo, Cheng Hsiang

AU - Shi, Guey Yueh

AU - Wu, Hua Lin

AU - Li, Yi Heng

PY - 2014/3/15

Y1 - 2014/3/15

N2 - Background Thrombomodulin (TM) is an endothelial cell (EC) membrane-bound anticoagulant protein that has novel direct cellular effects. TM is shed from EC and becomes soluble form (sTM) in plasma. Higher sTM levels in healthy subjects are associated with lower cardiovascular risk, suggesting that sTM possesses a protective role. The purpose of the study was to evaluate the effect of sTM on vascular endothelium. Methods and results Apoptosis of cultured ECs was induced via serum starvation. EC-bound TM was released into the medium after serum starvation. The medium conditioned by serum-starved EC decreased apoptosis in another set of cultured EC. Direct treatment with sTM reduced EC apoptosis and decreased pro-apoptotic protein expression. TM knockdown in EC exacerbated the rate of serum starvation-induced apoptosis. Treatment of sTM activated the phosphatidylinositol 3-kinase (PI3 kinase)-protein kinase B/Akt survival pathway and suppressed the death pathway, c-Jun N-terminal kinase. We found that sTM also increased growth and reduced apoptosis of endothelial progenitor cells. Conclusions EC-bound TM is released during stress-induced EC damage and becomes sTM, a paracrine factor that exerts anti-apoptotic activity. Our data indicate that sTM is not only an endothelial injury biomarker but also has cytoprotective effects on vascular endothelium.

AB - Background Thrombomodulin (TM) is an endothelial cell (EC) membrane-bound anticoagulant protein that has novel direct cellular effects. TM is shed from EC and becomes soluble form (sTM) in plasma. Higher sTM levels in healthy subjects are associated with lower cardiovascular risk, suggesting that sTM possesses a protective role. The purpose of the study was to evaluate the effect of sTM on vascular endothelium. Methods and results Apoptosis of cultured ECs was induced via serum starvation. EC-bound TM was released into the medium after serum starvation. The medium conditioned by serum-starved EC decreased apoptosis in another set of cultured EC. Direct treatment with sTM reduced EC apoptosis and decreased pro-apoptotic protein expression. TM knockdown in EC exacerbated the rate of serum starvation-induced apoptosis. Treatment of sTM activated the phosphatidylinositol 3-kinase (PI3 kinase)-protein kinase B/Akt survival pathway and suppressed the death pathway, c-Jun N-terminal kinase. We found that sTM also increased growth and reduced apoptosis of endothelial progenitor cells. Conclusions EC-bound TM is released during stress-induced EC damage and becomes sTM, a paracrine factor that exerts anti-apoptotic activity. Our data indicate that sTM is not only an endothelial injury biomarker but also has cytoprotective effects on vascular endothelium.

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