Abstract P2118: Intervention With The Adiponectin Mimetic Peptide ALY688 Protects Against Cardiac Dysfunction Induced By Ischemia Reperfusion Injury

Cardiac ischemia reperfusion injury is associated with significant morbidity and mortality for which there remains a great clinical unmet for effective therapeutics. Adiponectin mediates numerous cardioprotective effects and there has been significant interest in developing adiponectin-based therapeutics. The objective of this study was to evaluate the cardioprotective effect of ALY688 on myocardial remodelling at 48 hours post ischemia reperfusion injury, and cardiac function after 28 days. We used a rat model of myocardial ischemia for 45 min followed by reperfusion ± intravenous ALY688 administration during either ischemia or reperfusion followed by daily subcutaneous injection for 28 days. Acute phase (48h) analysis indicated that, compared with vehicle, ALY688 intervention during ischemia or reperfusion reduced cardiac injury indicated by circulating troponin I level, myocardial DNA oxidation and lipid peroxidation and in tissue sections we observed lower TUNEL staining, neutrophil infiltration and macrophage 1 polarization. Further analysis of inflammation indicated an increase of the pro-resolution cytokine IL-10 and Treg content via Foxp3 detection in animals treated with ALY688. Importantly, echocardiography indicated that after 14 and 28 days ALY688-treated animals had significantly improved cardiac function as well as reduced infarct size. This was associated with reduced fibrosis by Masson trichrome, scanning electron microscopy and established markers of fibrosis at the protein and mRNA level. Overall, our data provide strong evidence for the cardioprotective effects of adiponectin mimetic peptide ALY688 as a novel therapeutic strategy in treating ischemia reperfusion injury.