12 Post-ischemic myocardial remodeling and its modulation by an elastin-like recombinamers-based hydrog el

Heart failure caused by myocardial infarction (MI) is a burgeoning clinical problem. The modulation of post-ischemic remodelling after MI may ameliorate the deleterious effect of myocardial infarction on cardiac function. Elastin is a main component of the cardiac ECM and has critical functions in vasculature structures. We hypothesized that an elastin-like recombinamer-based (ELRs) hydrogel could benefit post-ischemic remodelling in an ovine model of MI. A novel ovine model of MI was developed to mimic patchy regional myocardial infarction often seen at coronary revascularization surgery early after NSTEMI (Non-ST Elevation Myocardial Infarction). Interventions were performed at seven days post-MI. One group was treated with the ELR hydrogel (n=6) and the other left untreated (n=6). All animals were sacrificed three weeks after intervention, after approval by the respective Institutional Ethics Committee. Functional data of ejection fraction (EF) and Fractional Shortening (FS) were obtained using transthoracic echocardiography prior to the induction of MI, one week later prior to intervention, and at three weeks after intervention prior to sacrifice. Masson’s Trichrome, anti-CD31 antibody and GS-I lectin were used for histology (n=5). Samples were analysed by confocal Raman microscopy (n=4). Fluorescent-labelled membrane proteins were incubated on a 48-lectin microarray (n=4) and were analysed by N-glycomics (n=6). RNA-sequencing was performed using an Illumina-HiSeq platform (n=3–4). A consistent average decrease in ejection fraction (EF) by 10.8%, 8.3% and 9% was seen seven days post-MI in MI-only, PBS and ELRs-hydrogel groups, respectively, with no significant difference across the groups (P=0.74). Remarkably, the decrease in EF due to MI was reversed only in the ELRs-treated group, which showed a statistically significant 16.2% average improvement (P