Stimulating myocardial regeneration with periostin Peptide in large mammals improves function post-myocardial infarction but increases myocardial fibrosis

• Published in: PloS one 2013-05, Vol.8 (5), p.e59656
• Main Authors: Ladage, Dennis, Yaniz-Galende, Elisa, Rapti, Kleopatra, Ishikawa, Kiyotake, Tilemann, Lisa, Shapiro, Scott, Takewa, Yoshiaki, Muller-Ehmsen, Jochen, Schwarz, Martin, Garcia, Mario J, Sanz, Javier, Hajjar, Roger J, Kawase, Yoshiaki
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis Inducing Agents - administration & dosage; Angiogenesis Inducing Agents - adverse effects; Angiogenesis Inducing Agents - pharmacology; Animals; Biology; Cardiology; Cardiomyocytes; Cardiomyopathy; Cell Adhesion Molecules - administration & dosage; Cell Adhesion Molecules - adverse effects; Cell Adhesion Molecules - pharmacology; Cell cycle; Cell Proliferation - drug effects; Cells, Cultured; Controlled release; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Drug Delivery Systems; Female; Fibroblasts; Fibrosis; Fibrosis - chemically induced; Gelatin Sponge, Absorbable; Growth factors; Heart; Heart - drug effects; Heart - physiopathology; Heart attack; Heart attacks; Heart diseases; Infarction; Livestock; Mammals; Medicine; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Myofibroblasts; Ostomy; Peptides; Polypeptides; Proteins; Regeneration; Rodents; Stem cells; Structure-function relationships; Sus scrofa; Swine; Ventricular Function, Left - drug effects; Veterinary Science
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059656

Mammalian myocardium has a finite but limited capacity to regenerate. Experimentally stimulating proliferation of cardiomyocytes with extracellular regeneration factors like periostin enhances cardiac repair in rodents. The aim of this study was to develop a safe method for delivering regeneration factors to the heart and to test the functional and structural effects of periostin peptide treatment in a large animal model of myocardial infarction (MI). We developed a controlled release system to deliver recombinant periostin peptide into the pericardial space. A single application of this method was performed two days after experimental MI in swine. Animals were randomly assigned to receive either saline or periostin peptide. Experimental groups were compared at baseline, day 2, 1 month and 3 months. Treatment with periostin peptide increased the EF from 31% to 41% and decreased by 22% the infarct size within 12 weeks. Periostin peptide-treated animals had newly formed myocardium strips within the infarct scar, leading to locally improved myocardial function. In addition the capillary density was increased in animals receiving periostin. However, periostin peptide treatment increased myocardial fibrosis in the remote region at one week and 12 weeks post-treatment. Our study shows that myocardial regeneration through targeted peptides is possible. However, in the case of periostin the effects on cardiac fibrosis may limit its clinical application as a viable therapeutic strategy.