Cardioprotective actions of the annexin-A1 N-terminal peptide, AC2-26, against myocardial infarction

Cheng Xue Qin, Sarah Rosli, Minh Deo, Nga Cao, Jesse Walsh, Mitchel Tate, Amy E. Alexander, Daniel Donner, Duncan Horlock, Renming Li, Helen Kiriazis, Man K.S. Lee, Jane E. Bourke, Yuan Yang, Andrew J. Murphy, Xiao-Jun Du, Xiao Ming Gao, Rebecca H. Ritchie

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7 Citations (Scopus)

Abstract

The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) in vivo. Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac2-26, particularly beyond its anti-necrotic actions in the first few hours after an ischemic insult. In this study, we tested the hypothesis that exogenous Ac2-26 limits cardiac injury in vitro and in vivo. Firstly, we demonstrated that Ac2-26 limits cardiomyocyte death both in vitro and in mice subjected to ischemia-reperfusion (I-R) injury in vivo (Ac2-26, 1 mg/kg, i.v. just prior to post-ischemic reperfusion). Further, Ac2-26 (1 mg/kg i.v.) reduced cardiac inflammation (after 48 h reperfusion), as well as both cardiac fibrosis and apoptosis (after 7-days reperfusion). Lastly, we investigated whether Ac2-26 preserved cardiac function after MI. Ac2-26 (1 mg/kg/day s.c., osmotic pump) delayed early cardiac dysfunction 1 week post MI, but elicited no further improvement 4 weeks after MI. Taken together, our data demonstrate the first evidence that Ac2-26 not only preserves cardiomyocyte survival in vitro, but also offers cardioprotection beyond the first few hours after an ischemic insult in vivo. Annexin-A1 mimetics thus represent a potential new therapy to improve cardiac outcomes after MI.

Original languageEnglish
Article number269
Number of pages16
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 3 Apr 2019

Keywords

  • Annexin-A1
  • Cardiac remodeling
  • Formyl peptide receptors
  • Inflammation
  • Myocardial ischemia

Cite this

Qin, C. X., Rosli, S., Deo, M., Cao, N., Walsh, J., Tate, M., Alexander, A. E., Donner, D., Horlock, D., Li, R., Kiriazis, H., Lee, M. K. S., Bourke, J. E., Yang, Y., Murphy, A. J., Du, X-J., Gao, X. M., & Ritchie, R. H. (2019). Cardioprotective actions of the annexin-A1 N-terminal peptide, AC2-26, against myocardial infarction. Frontiers in Pharmacology, 10, [269]. https://doi.org/10.3389/fphar.2019.00269