Targeting Cardiac Inflammation Post Mi to Limit Cardiac Necrosis and Contractile Dysfunction

Myocardial infarction (MI) and the resultant heart failure remain a major cause of death, despite clinical advances such as thrombolysis and percutaneous revascularisation interventions. These treatments have focused on restoring blood flow to the ischaemic tissue to prevent tissue necrosis and preserve organ function in the very short-term (hours). Myocardial injury however continues to evolve over days and weeks post MI, with adverse cardiac remodelling and cardiac contractile dysfunction ultimately progressing to heart failure. Development of new therapeutic strategies for treating MI after the event (while the injury is still evolving), alone or concurrent with standard care, is thus urgently warranted, to reduce progression to heart failure and death in affected patients post MI. Targeting annexin-A1/formyl peptide receptor (FPR) mechanisms, integral to regulation of inflammation and its resolution may represent one such potential therapeutic approach. Our work provided the first evidence of the direct protective annexin-A1/FPR actions on myocardium, which now encompass cardioprotective actions of both endogenous peptide and exogenous small-molecule ligands, These approaches target cardiac necrosis, inflammation, remodelling and contractile dysfunction both in vitro and in vivo over the short- and longer-term, and provide new avenues for development of annexin-A1/FPR-pharmacotherapies for improving outcome after myocardial infarction and other cardiac inflammatory disorders.