Cardioprotective Actions of the Annexin-A1 N-Terminal Peptide, Ac, Against Myocardial Infarction.

The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) . Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac, particularly beyond its anti-necrotic actions in the first few hours after an ischemic insult. In this study, we tested the hypothesis that exogenous Ac limits cardiac injury and Firstly, we demonstrated that Ac limits cardiomyocyte death both and in mice subjected to ischemia-reperfusion (I-R) injury (Ac 1 mg/kg, i.v. just prior to post-ischemic reperfusion). Further, Ac (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 Ac preserved cardiac function after MI. Ac (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 Ac not only preserves cardiomyocyte survival , but also offers cardioprotection beyond the first few hours after an ischemic insult . Annexin-A1 mimetics thus represent a potential new therapy to improve cardiac outcomes after MI.