Journal article
Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance
The EMBO journal, Vol.41(9), pp.e109890-n/a
05/02/2022
DOI: 10.15252/embj.2021109890
PMID: 35243676
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.
Details
- Title: Subtitle
- Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance
- Creators
- Heon-Woo Lee - Yale UniversityYanying Xu - Central South UniversityXiaolong Zhu - Yale UniversityCholsoon Jang - University of California, IrvineWoosoung Choi - Gwangju Institute of Science and TechnologyHosung Bae - University of California, IrvineWeiwei Wang - W. M. Keck FoundationLiqun He - Uppsala UniversitySuk-Won Jin - Gwangju Institute of Science and TechnologyZoltan Arany - University of PennsylvaniaMichael Simons - Yale University
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.41(9), pp.e109890-n/a
- DOI
- 10.15252/embj.2021109890
- PMID
- 35243676
- NLM abbreviation
- EMBO J
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Grant note
- R01 HL135582 / NHLBI NIH HHS P01 HL107205 / NHLBI NIH HHS R01 HL062289 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/02/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217132202771
Metrics
2 Record Views