The inhibition in tumor necrosis factor-α-induced attenuation in endothelial thrombomodulin expression by carvedilol is mediated by nuclear factor-κB and reactive oxygen species

Pen-Yuan Lin, Hsi Che Shen, Chien Jen Chen, Shu En Wu, Hsien Li Kao, Jen-Hung Huang, Danny Ling Wang, Shih-Chung Chen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Carvedilol, a nonselective β-adrenoceptor antagonist, has been shown to possess antioxidant effects and reduce the risk of hospitalization and death in patients with severe congestive heart failure, which is featured by the activation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), and leads to thrombotic complications. Thrombomodulin (TM) plays protective roles against thrombosis. Treatment of ECs with TNF-α resulted in a down-regulation in the TM expression in a time-dependent manner. Pre-treatment of ECs with carvedilol (1 and 10 μM) for 1 h significantly up-regulated the TM expression in ECs in response to TNF-α. When ECs were pre-treated with a nuclear factor-κB (NF-κB) inhibitor, i.e., parthenolide, their TNF-α-mediated down-regulation of TM expression was inhibited. Pre-treatment of ECs with carvedilol inhibited the NF-κB-DNA binding activity in ECs induced by TNF-α. Our findings provide insights into the mechanisms by which carvedilol exerts anti-thrombotic effects by inducing TM expression in ECs in response to pro-inflammatory stimulation.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalJournal of Thrombosis and Thrombolysis
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Carvedilol
  • Endothelial cell
  • Reactive oxygen species
  • Thrombomodulin
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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