title: Stimulating myocardial regeneration with periostin Peptide in large mammals improves function post-myocardial infarction but increases myocardial fibrosis.
abstract: OBJECTIVE
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Research Center, Department of Cardiology, Mount Sinai School of Medicine, New York, New York, USA. dennis.ladage@mssm.edu
authors.forename: Dennis
authors.initials: D
authors.lastname: Ladage
authors.forename: Elisa
authors.initials: E
authors.lastname: Yaniz-Galende
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Rapti
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Tilemann
authors.forename: Scott
authors.initials: S
authors.lastname: Shapiro
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takewa
authors.forename: Jochen
authors.initials: J
authors.lastname: Muller-Ehmsen
authors.forename: Martin
authors.initials: M
authors.lastname: Schwarz
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Garcia
authors.forename: Javier
authors.initials: J
authors.lastname: Sanz
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawase
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D016503:Drug Delivery Systems; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D005781:Gelatin Sponge, Absorbable; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D058628:Myofibroblasts; D012038:Regeneration; D034421:Sus scrofa; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human