Article

Journal of Cardiovascular Translational Research

, Volume 5, Issue 5, pp 654-665

The Hypoxic Epicardial and Subepicardial Microenvironment

  • Fatih KocabasAffiliated withDepartment of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center
  • , Ahmed I. MahmoudAffiliated withDepartment of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center
  • , Drazen SosicAffiliated withDepartment of Molecular Biology, UT Southwestern Medical Center
  • , Enzo R. PorrelloAffiliated withDepartment of Molecular Biology, UT Southwestern Medical Center
  • , Rui ChenAffiliated withDepartment of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center
  • , Joseph A. GarciaAffiliated withDepartment of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center
  • , Ralph J. DeBerardinisAffiliated withDepartments of Pediatrics and Genetics, UT Southwestern Medical Center
  • , Hesham A. SadekAffiliated withDepartment of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center Email author 

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Abstract

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.

Keywords

Epicardium Subepicardium Cardiac progenitors Hypoxic microenvironment