Brain Endothelial Cell Bioenergetics via Extracellular Flux Analysis

Abstract

The neurovascular unit (NVU) is an important functional component in the central nervous system (CNS). The NVU consists of multiple cell types (endothelial cells, pericytes, astrocytes, others) working together as a restrictive blood‐tissue interface and functions to maintain homeostasis within nervous tissue in the CNS. A dysfunctional NVU is associated with many disease states, including Alzheimer's Disease, strokes, and tumors. The endothelial cell is an important barrier‐forming cell of the NVU because of its direct contact with the blood, its intercellular tight junctions, biotransforming enzymes, and asymmetric distribution of active and carrier‐mediated transporters. These properties are important for maintaining the neuro‐microenvironment and require an abundant supply of energy (ATP). Although energy metabolism has been studied in various tissues and cells, little is known about the energy producing pathways of brain endothelial cells. Therefore, using extracellular flux analysis, we characterized the bioenergetics of human brain microvascular endothelial cells (BMECs) in vitro. BMECs are primarily glycolytic and D‐glucose, pyruvate, and glutamine are preferred metabolic substrates. Inhibitors of monocarboxylate transporter (MCT1), mitochondrial pyruvate carrier, and glycolysis significantly alter ATP production, cellular respiration, and/or glycolytic rates. These findings contribute to our understanding of endothelial cell metabolic plasticity in normal and diseased brain as well as active angiogenesis during development or tumorigenesis. Understanding endothelial cell bioenergetics will be useful for future studies regarding development of therapies, that target endothelial cell energetics, for neurological disorders.Support or Funding InformationWhiteside Foundation and the Department of DefenseThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.