Abstract 623: A Novel Strategy For Reducing Future Events In Myocardial Infarction Survivors

Objective: Myocardial infarction (MI) is the primary cause of ischaemic heart disease. ApoA-I, the main apolipoprotein constituent of high-density lipoproteins (HDLs) has anti-inflammatory properties and protects against post-MI ischemia/reperfusion (I/R) injury. However, HDLs from MI survivors do not protect against I/R injury. This study asks whether a newly developed peptide that has anti-inflammatory properties can mimic the ability of apoA-I to reduce I/R injury in a rat model of MI, and protect myocardial fibroblasts from hypoxic damage. Methods: The left anterior descending (LAD) coronary artery of Wistar rats (n≥6/group) was temporarily ligated for 1 h to induce I/R injury. Rats that underwent the procedure were randomly allocated to no treatment or treatment with PBS or peptide. The procedure was also performed on rats without LAD ligation (sham control). The rats were treated immediately after the procedure with peptide (10 mg/kg, ip) or PBS, then re-treated every second day for 7 days. H9C2 myocardial fibroblasts were incubated for 24 h under hypoxic (0.4 % oxygen) conditions ± peptide (0.05-1 mg/ml). Results: Peptide treatment improved the ejection fraction of rats that underwent LAD ligation by 16.4±7% (p<0.05) compared to control. It also reduced fibrosis in the left ventricle by 12.6±2.6% (p<0.0001). These results were recapitulated in vitro in myocardial fibroblasts incubated under hypoxic conditions, with peptide treatment (1 mg/ml) decreasing cell death by 19.8±4.0% (p<0.05). Conclusions: The peptide protects myocardial cell viability and reduces myocardial death and is therefore of potential therapeutic benefit for MI survivors with I/R injury.