Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction

Yi Heng Li, Hsing Chun Chung, Chawn Yau Luo, Ting Hsing Chao, Kou Gi Shyu, Guey Yueh Shi, Hua Lin Wu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Cardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction. Thrombomodulin (TM), an endothelial anticoagulant protein, was found to have direct effects on cellular proliferation and inflammation. We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance. Methods and Results: TM expression was evaluated in cardiomyocytes from hearts of mice that underwent transverse aortic constriction (TAC). The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined. Recombinant TM protein was administered continuously in mice that underwent TAC, and serial LV function was determined. There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice. TM treatment decreased doxorubicin-induced apoptosis of cardiomyocytes and increased the Bcl-2/Bax ratio. It also increased cardiomyocytes hypertrophy, expression of atrial natriuretic peptide, and significantly activated the extracellular signal-regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt) signaling pathways in cardiomyocytes. Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice. Conclusions: TM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload.

Original languageEnglish
Pages (from-to)980-990
Number of pages11
JournalJournal of Cardiac Failure
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Cardiac hypertrophy
  • Heart failure
  • Thrombomodulin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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