TY - JOUR T1 - Agrin promotes coordinated therapeutic processes leading to improved cardiac repair in pigs JF - bioRxiv DO - 10.1101/854372 SP - 854372 AU - Andrea Baehr AU - Kfir Baruch Umansky AU - Elad Bassat AU - Katharina Klett AU - Victoria Jurisch AU - Tarik Bozoglu AU - Nadja Hornaschewitz AU - Olga Solyanik AU - David Kain AU - Bartolo Ferrero AU - Renee Cohen-Rabi AU - Markus Krane AU - Clemens Cyran AU - Oliver Soehnlein AU - Karl Ludwig Laugwitz AU - Rabea Hinkel AU - Christian Kupatt AU - Eldad Tzahor Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/25/854372.abstract N2 - Ischemic heart diseases are classified among the leading cause of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a significant number of MI patients develop chronic heart failure over time. We have recently reported that a fragment of the extra cellular matrix (ECM) protein Agrin promotes cardiac regeneration following MI in adult mice. Here, we tested the therapeutic potential of Agrin in a preclinical porcine model, comprising either 3 or 28 days (d) reperfusion period. We first demonstrate that local (antegrade) delivery of recombinant human Agrin (rhAgrin) to the infarcted pig heart can target the affected regions in an efficient and clinically-relevant manner. Single dose of rhAgrin resulted in significant improvement in heart function, infarct size, fibrosis and adverse remodeling parameters 28 days post MI. Short-term MI experiment along with complementary murine MI studies revealed myocardial protection, improved angiogenesis, inflammatory suppression and cell cycle re-entry, as Agrin’s mechanisms of action. We conclude that a single dose of Agrin is capable of reducing ischemia reperfusion injury and improving cardiac function, demonstrating that Agrin could serve as a therapy for patients with acute MI and potentially heart failure. ER -