title: Cardioprotective potential of annexin-A1 mimetics in myocardial infarction.
abstract: Myocardial infarction (MI) and its resultant heart failure remains a major cause of death in the world. The current treatments for patients with MI are revascularization with thrombolytic agents or interventional procedures. These treatments have focused on restoring blood flow to the ischemic tissue to prevent tissue necrosis and preserve organ function. The restoration of blood flow after a period of ischemia, however, may elicit further myocardial damage, called reperfusion injury. Pharmacological interventions, such as antioxidant and Ca(2+) channel blockers, have shown premises in experimental settings; however, clinical studies have shown limited success. Thus, there is a need for the development of novel therapies to treat reperfusion injury. The therapeutic potential of glucocorticoid-regulated anti-inflammatory mediator annexin-A1 (ANX-A1) has recently been recognized in a range of systemic inflammatory disorders. ANX-A1 binds to and activates the family of formyl peptide receptors (G protein-coupled receptor family) to inhibit neutrophil activation, migration and infiltration. Until recently, studies on the cardioprotective actions of ANX-A1 and its peptide mimetics (Ac2-26, CGEN-855A) have largely focused on its anti-inflammatory effects as a mechanism of preserving myocardial viability following I-R injury. Our laboratory provided the first evidence of the direct protective action of ANX-A1 on myocardium, independent of inflammatory cells in vitro. We now review the potential for ANX-A1 based therapeutics to be seen as a "triple shield" therapy against myocardial I-R injury, limiting neutrophil infiltration and preserving both cardiomyocyte viability and contractile function. This novel therapy may thus represent a valuable clinical approach to improve outcome after MI.
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Chengxue
authors.initials: C
authors.lastname: Qin
authors.affiliation: Centre for Inflammatory Diseases Monash University and Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Yuan H
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, and Department of Pharmacology, Monash University, Parkville, Victoria, Australia.
authors.forename: Lauren
authors.initials: L
authors.lastname: May
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tu
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora 3083, Victoria, Australia.
authors.forename: Owen L
authors.initials: OL
authors.lastname: Woodman
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia. Electronic address: rebecca.ritchie@bakeridi.edu.au.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Ritchie
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000378:metabolism
chemical_list: D017305:Annexin A1; D002316:Cardiotonic Agents; D044042:Receptors, Formyl Peptide
keywords: Ac2-26; Cardiomyopathy; Cardioprotection; Formyl peptide receptors; Inflammation; Ischemia–reperfusion