Recombinant human annexin A5 can repair the disrupted cardiomyocyte adherens junctions in endotoxemia

Changping Gu, Mengjie Liu, Tao Zhao, Lijie Zhai, Yuelan Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Recombinant human annexin A5 (Anx5) is known to protect cardiac function during endotoxemia, although the underlying mechanisms have yet to be elucidated. In this study, we demonstrated that Anx5 could repair the disrupted cardiomyocyte adherens junctions and improve the myocardial contractile function in lipopolysaccharide (LPS)-induced endotoxemia. Mechanistic studies revealed that Anx5 could antagonize the disassociation between p120-catenin (p120) and N-cadherin as well as the dephosphorylation of p120 in LPS-treated cardiomyocytes. Small interference RNA and specific inhibitors experiment demonstrated that Anx5 regulated p120 functions by inhibition of p21-activated kinase 5 in a protein kinase Cα-dependent way. Moreover, Anx5 could inhibit nuclear factor κB activation and downregulate the level of inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β, which contributed to improving tissue pathological damage in LPS-induced mouse endotoxemia model. Taken together, Anx5 could protect cardiomyocytes adherens junctions and improve myocardial contractile function via regulation of p120 and anti-inflammation in LPS-induced endotoxemia. This study provided novel insights in the prevention and treatment of septic shock.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalShock
Volume44
Issue number1
DOIs
StatePublished - Jul 15 2015

Keywords

  • Adherens junctions
  • annexin A5
  • endotoxemia
  • p120
  • PAK5
  • PKCα

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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