Abstract 15121: Induction of an Embryonic Cell Program After Myocardial Infarction in Non-Cardiomyocytes - Cardiac Resident Stem Cells or Fibroblasts?
Introduction: The existence of activated cardiac resident stem cells after myocardial infarction (MI) is still subject of controversial discussion.
Hypothesis: We hypothesized that the adult mammalian heart harbors a non-cardiomyocyte population with a reemerging embryonic gene expression program after MI.
Methods and Results: The Nkx2.5 cardiac enhancer (CE) specifically marks cardiac progenitor cells during murine embryonic development whereas it is inactive in adult mice (> 3 weeks). However, the induction of acute MI by permanent LAD ligation led to the recurrence of 0.5% GFP+ cells in adult Nkx2.5 CE GFP mice one week after MI. Reemerging GFP+ cells were identified in the infarction area and border zone. Several cardiac developmental markers (Gata4, Tbx5, Baf60c) were upregulated in the GFP+ compared to the GFP negative cell fraction of the heart. However, myo-/fibroblast markers (FAP, Myh10, Acta2) were also highly expressed in the GFP+ cells but no evidence for cardiomyocyte properties was found (Myl2, Tnnt2). Detailed expression profiling by micro array analysis revealed GO-terms like inflammatory response and extracellular matrix for the GFP+ cells. Q-PCR confirmed an up-regulation of Il6, Col3a1 and Tgfbr2, typical markers for myofibroblasts. Interestingly, GFP+ cells also emerged in a non-ischemic model of heart failure by transverse aortic constriction and in heterotopic transplanted hearts after ischemia-reperfusion injury, consistent with the activation time course of myofibroblasts in these models. Additionally, cross over transplantation of wild type hearts into Nkx2.5 CE GFP mice revealed the resident cardiac origin of the GFP+ cells.
Conclusion: In conclusion, the adult mouse heart exhibited reemerging activated non-cardiomyocytes with an embryonic signature after MI. However, this cell population seemed to be part of the inflammatory reaction and showed a phenotype similar to activated myo-/fibroblasts rather than to activated resident cardiac stem cells.
Author Disclosures: S. Doppler: None. M. Deutsch: None. X. Li: None. T. Ratschiller: None. H. Lahm: None. C. Jerrentrup: None. G. Santamaria: None. M. Dreßen: None. S. Wu: None. R. Lange: None. M. Krane: None.
- © 2016 by American Heart Association, Inc.