Stimulating Myocardial Regeneration with Periostin Peptide in Large Mammals Improves Function Post-Myocardial Infarction but Increases Myocardial Fibrosis

Dennis Ladage, Elisa Yaniz-Galende, Kleopatra Rapti, Kiyotake Ishikawa, Lisa Tilemann, Scott Shapiro, Yoshiaki Takewa, Jochen Muller-Ehmsen, Martin Schwarz, Mario J. Garcia, Javier Sanz, Roger J. Hajjar, Yoshiaki Kawase

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Aims: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).Methods and 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.Conclusion: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.

Original languageEnglish (US)
Article numbere59656
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 20 2013
Externally publishedYes

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Mammals
myocardial infarction
fibrosis
Regeneration
Fibrosis
Myocardial Infarction
peptides
mammals
Peptides
Animals
infarction
myocardium
Myocardium
animals
Pericardium
application methods
Cardiac Myocytes
Cicatrix
Rodentia
Repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Stimulating Myocardial Regeneration with Periostin Peptide in Large Mammals Improves Function Post-Myocardial Infarction but Increases Myocardial Fibrosis. / 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.

In: PLoS One, Vol. 8, No. 5, e59656, 20.05.2013.

Research output: Contribution to journalArticle

Ladage, D, Yaniz-Galende, E, Rapti, K, Ishikawa, K, Tilemann, L, Shapiro, S, Takewa, Y, Muller-Ehmsen, J, Schwarz, M, Garcia, MJ, Sanz, J, Hajjar, RJ & Kawase, Y 2013, 'Stimulating Myocardial Regeneration with Periostin Peptide in Large Mammals Improves Function Post-Myocardial Infarction but Increases Myocardial Fibrosis', PLoS One, vol. 8, no. 5, e59656. https://doi.org/10.1371/journal.pone.0059656
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. / Stimulating Myocardial Regeneration with Periostin Peptide in Large Mammals Improves Function Post-Myocardial Infarction but Increases Myocardial Fibrosis. In: PLoS One. 2013 ; Vol. 8, No. 5.
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AU - Ishikawa, Kiyotake

AU - Tilemann, Lisa

AU - Shapiro, Scott

AU - Takewa, Yoshiaki

AU - Muller-Ehmsen, Jochen

AU - Schwarz, Martin

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