한빛사논문
Heon-Woo Lee1,†, Yanying Xu1,2,†, Xiaolong Zhu1, Cholsoon Jang3, Woosung Choi4,Hosung Bae3, Weiwei Wang5, Liqun He6, Suk-Won Jin1,4, Zoltan Arany7 & Michael Simons1,8,*
1Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China 3Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA 4School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea 5W. M. Keck Biotechnology Resource Laboratory, Yale University School of Medicine, New Haven, CT, USA 6Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden 7Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 8Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA
*Corresponding author.
†These authors contributed equally to this work.
Abstract
Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial–pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood–brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood–brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.
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