Metabolic and Redox Regulation of Cardiovascular Stem Cell Biology and Pathology

Significance: Cardiovascular stem cells are important for regeneration and repair of damaged tissue. Recent Advances: Pluripotent stem cells have a unique metabolism, which is adopted for their energetic and biosynthetic demand as rapidly proliferating cells. Stem cell differentiation requires an exceptional metabolic flexibility allowing for metabolic remodeling between glycolysis and oxidative phosphorylation. Critical Issues: Respiration is associated with the generation of reactive oxygen species (ROS) by the mitochondrial respiratory chain. But also the membrane-bound protein nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) contributes to ROS levels. ROS not only play a significant role in stem cell differentiation and tissue renewal but also cause senescence and contribute to tissue aging. Future Directions: For utilization of stem cells in therapeutic approaches, a deep understanding of the molecular mechanisms how metabolism and the cellular redox state regulate stem cell differentiation is required. Modulating the redox state of stem cells using antioxidative agents may be suitable to enhance activity of endothelial progenitor cells.