Fibronectin is essential for reparative cardiac progenitor cell response after myocardial infarction

Mathias H. Konstandin, Haruhiro Toko, Grady M. Gastelum, Pearl Quijada, Andrea De La Torre, Mercedes Quintana, Brett Collins, Shabana Din, Daniele Avitabile, Mirko Völkers, Natalie Gude, Reinhard Fässler, Mark A. Sussman

Research output: Contribution to journalArticle

Abstract

RATIONALE:: Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application, despite limited mechanistic understanding of the endogenous response after myocardial infarction (MI). Extracellular matrix undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. OBJECTIVE:: To demonstrate the significance of fibronectin (Fn), a component of the extracellular matrix, for induction of the endogenous CPC response to MI. METHODS AND RESULTS:: This report shows that presence of CPCs correlates with the expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery were evident at the end of a 12-week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via β1-integrin-focal adhesion kinase-signal transducer and activator of transcription 3-Pim1 independent of Akt. CONCLUSIONS:: Fn is essential for endogenous CPC expansion and repair required for stabilization of cardiac function after MI.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalCirculation Research
Volume113
Issue number2
DOIs
Publication statusPublished - Jul 5 2013

Keywords

  • adult stem cells
  • cell adhesion molecules fibronectins
  • myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Konstandin, M. H., Toko, H., Gastelum, G. M., Quijada, P., De La Torre, A., Quintana, M., Collins, B., Din, S., Avitabile, D., Völkers, M., Gude, N., Fässler, R., & Sussman, M. A. (2013). Fibronectin is essential for reparative cardiac progenitor cell response after myocardial infarction. Circulation Research, 113(2), 115-125. https://doi.org/10.1161/CIRCRESAHA.113.301152