Abstract 3231: Recombinant Periostin Peptide Improves Myocardial Function and Decreases Scar Size in a Preclinical Infarct Model
Replacing lost cardiomyocytes using regenerative strategies would offer a revolutionary strategy for the treatment of heart failure. We previously demonstrated that administration of recombinant periostin peptide induces cardiomyocyte replacement in a rat infarct model. Here, we report the results of a pre-clinical trial of periostin peptide administration in a porcine myocardial infarction model. We induced myocardial infarction in Yorkshire swine by deploying a coil in the left anterior descending coronary artery. Using a pericardiocentesis approach, we applied periostin fasciclin I-only polypeptide with a Gelfoam-based delivery system for sustained release into the pericardial space 2 days after myocardial infarction. We determined the effect on cardiac function before, 2 days after, 1 month after, and 3 months after initiation of therapy. Control (n=6) and treatment groups (n=7) were comparable in their hemodynamic parameters as well as the extent of myocardial infarction before beginning of therapy (Tab. 1⇓). Ejection fraction, determined by 2D-echocardiography, improved in periostin-treated group at one month after periostin administration (48.0±2.3%) compared to control (38.5±5.0%). Left ventricular catherization showed a significantly increased dP/dt in periostin-treated animals after one month (1709±130 vs. 1355±98 mmHg/s). Similarly after one month cardiac index was increased (114±5.3 vs. 98±10 mL/kg/min). Gain of function in the periostin group was preserved over three months, consistent with a smaller scar volume measured by cMRI and TTC staining (90±11 vs. 127±14 mm3). In summary, minimally invasive application of cardiac regeneration factors is effective and safe. A single dose of periostin peptide induced sustained improvement of cardiac function after myocardial infarction. Overall, inducing myocardial regeneration with recombinant periostin is a promising strategy for the treatment of ischemic heart disease.