Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance.
Heon-Woo LeeYanying XuXiaolong ZhuCholsoon JangWoosoung ChoiHosung BaeWeiwei WangLiqun HeSuk-Won JinZoltan AranyMichael SimonsPublished in: The EMBO journal (2022)
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.
Keyphrases
- blood brain barrier
- endothelial cells
- metabolic syndrome
- nitric oxide
- cerebral ischemia
- end stage renal disease
- amino acid
- healthcare
- ejection fraction
- stem cells
- adipose tissue
- mesenchymal stem cells
- brain injury
- multiple sclerosis
- high glucose
- skeletal muscle
- vascular endothelial growth factor
- patient reported outcomes
- resting state
- functional connectivity
- case control