Metabolic Flexibility and Dysfunction in Cardiovascular Cells

C ardiovascular cells that contribute directly to atheroscle- rosis and cardiac dysfunction are known to exhibit metabolic flexibility, characterized by the ability to switch from generating ATP primarily through oxidative phosphorylation to using glycolysis as the predominate energy source, and to shift from one fuel source to another. This flexibility occurs in endothelial cells (ECs), myeloid cells, and cardiomyocytes during normal development and physiology, and is thought to have evolved to protect cells with heightened energy demand from the increased oxidative stress that can be a result of oxidative phosphorylation, 1 to shunt glucose to side branches of glycolysis, 2 to provide energy more rapidly, 1 or to use the most abundant fuel available. With the growing problem of systemic nutrient overload and associated insulin resistance, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, metabolic flexibility and dysfunction in cells involved in cardiovascular disease have received increased attention as possible contributors to systemic inflammation and cardiovascular risk associated with these states.