Unique energetic profile of cardiac progenitor cells

Background Cardiac progenitor cells (CPCs) provide a promising avenue for the treatment of heart failure; however, little is known about their metabolism and how diabetes affects their reparative abilities. Methods/Results Energetics in CPCs (c‐kit + /lin − ) were measured by extracellular flux analysis and compared with adult cardiac myocytes (CMCs). CPCs demonstrated a highly active respiratory chain, characterized by a low mitochondrial reserve capacity and a mitochondrial membrane potential (ΔΨ) similar to that of uncoupled (i.e., FCCP‐treated) cells. Despite this low ΔΨ, the respiratory control ratio for CPCs was 8.4 while for CMCs it was 6; the majority of O 2 consumption in CPCs was linked to ATP production. CPCs also demonstrated a high glycolytic rate and predominantly insulin‐independent glucose utilization, as measured by increases in glycolytic flux upon treatment with glucose (0–27.5 mM) or insulin (100 nM). Hyperglycemia decreased CPC proliferation by 40% compared with cells incubated under normoglycemic conditions. Conclusions CPCs demonstrate a unique bioenergetic signature characterized by a highly coupled respiratory chain, low mitochondrial ΔΨ, and a high glycolytic rate. These cells appear to be exquisitely sensitive to extracellular glucose concentration, indicating that diabetes could lead to deleterious changes in the cardiac stem cell population. Financial support: NIH