The hypoxic epicardial and subepicardial microenvironment

Fatih Kocabas, Ahmed I. Mahmoud, Drazen Sosic, Enzo R. Porrello, Rui Chen, Joseph A. Garcia, Ralph J. Deberardinis, Hesham A. Sadek

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Recent reports indicate that the adult mammalian heart is capable of limited, but measurable, cardiomyocyte turnover. While the lineage origin of the newly formed cardiomyocytes is not entirely understood, mounting evidence suggest that the epicardium and subepicardium may represent an important source of cardiac stem or progenitor cells. Stem cell niches are characterized by low oxygen tension, where stem cells preferentially utilize cytoplasmic glycolysis to meet their energy demands. However, it is unclear if the heart harbors similar hypoxic regions, or whether these regions house metabolically distinct cardiac progenitor populations. Here we identify the epicardium and subepicardium as the cardiac hypoxic niche-based capillary density quantification, and localization of Hif-1α in the uninjured heart. We further demonstrate that this hypoxic microenvironment houses a metabolically distinct population of glycolytic progenitor cells. Finally, we show that Hif-1α regulates the glycolytic phenotype and progenitor properties of these cells. These findings highlight important anatomical and functional properties of the epicardial and subepicardial microenvironment, and the potential role of hypoxia signaling in regulation of cardiac progenitors.

Original languageEnglish (US)
Pages (from-to)654-665
Number of pages12
JournalJournal of cardiovascular translational research
Issue number5
StatePublished - Oct 2012


  • Cardiac progenitors
  • Epicardium
  • Hypoxic microenvironment
  • Subepicardium

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)


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