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

Ting Hsing Chao, Wei Chuan Tsai, Ju Yi Chen, Ping Yen Liu, Hsing Chun Chung, Shi Ya Tseng, Cheng Hsiang Kuo, Guey Yueh Shi, Hua Lin Wu, Yi Heng Li

研究成果: Article同行評審

19 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)340-349
期刊International Journal of Cardiology
出版狀態Published - 2014 3月 15

All Science Journal Classification (ASJC) codes

  • 心臟病學與心血管醫學


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