Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity.

AMP-Activated Protein Kinases / metabolism Animals Blood-Brain Barrier / physiology Brain / blood supply Cell Movement Cell Proliferation Endothelial Cells / metabolism Endothelium Endothelium, Vascular / physiology Energy Metabolism Glucose / metabolism Glucose Transporter Type 1 / antagonists & inhibitors Glycolysis Humans Mice Neovascularization, Physiologic Retina / cytology Retinal Vessels
blood-brain barrier endothelium extracellular matrix glucose transport glycolysis homeostasis

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
31 07 2020
Historique:
pubmed: 15 5 2020
medline: 22 5 2021
entrez: 15 5 2020
Statut: ppublish

Résumé

Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/ We evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB. Inhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets. GLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.

Identifiants

DOI: 10.1161/CIRCRESAHA.119.316463 PMID: 32404031 PMC: PMC7386868
pubmed: 32404031
doi: 10.1161/CIRCRESAHA.119.316463
pmc: PMC7386868
doi:

Substances chimiques

Glucose Transporter Type 1 0
SLC2A1 protein, human 0
Slc2a1 protein, mouse 0
AMP-Activated Protein Kinases EC 2.7.11.31
Glucose IY9XDZ35W2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

466-482

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Auteurs

Koen Veys (K)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.

Zheng Fan (Z)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).

Moheb Ghobrial (M)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich (UZH) and ETHZ and Division of Neurosurgery, USZ, Zurich (M.G., T.W.).

Ann Bouché (A)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.

Melissa García-Caballero (M)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.

Kim Vriens (K)

Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology (K. Vriens, S.-M.F.), KU Leuven.
Laboratory of Cellular Metabolism and Metabolic Regulation (K. Vriens, S.-M.F.), Center for Cancer Biology, VIB, Leuven.

Nadine Vasconcelos Conchinha (NV)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.

Aline Seuwen (A)

Institute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, UZH, Zurich, Switzerland (A. Seuwen, F.S., A. Schroeter).

Felix Schlegel (F)

Institute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, UZH, Zurich, Switzerland (A. Seuwen, F.S., A. Schroeter).

Tatiane Gorski (T)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).

Melissa Crabbé (M)

Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
Molecular Small Animal Imaging Centre, KU Leuven (M.C., C.C., K.V.L.).

Paola Gilardoni (P)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).

Raphaela Ardicoglu (R)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).

Johanna Schaffenrath (J)

Neuroscience Center Zurich (J.S., A.K.), UZH/ETHZ, Zurich, Switzerland.
Department of Neurosurgery, Clinical Neurocentre, USZ, Zurich (J.S., A.K.).

Cindy Casteels (C)

Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
Molecular Small Animal Imaging Centre, KU Leuven (M.C., C.C., K.V.L.).

Gino De Smet (G)

Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Vrije Universiteit Brussel (G.D.S., I.S.).

Ilse Smolders (I)

Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Vrije Universiteit Brussel (G.D.S., I.S.).

Koen Van Laere (K)

Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
Molecular Small Animal Imaging Centre, KU Leuven (M.C., C.C., K.V.L.).

E Dale Abel (ED)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Fraternal Order of Eagles Diabetes Research Center (E.D.A.), University of Iowa.
Division of Endocrinology and Metabolism, Carver College of Medicine (E.D.A.), University of Iowa.

Sarah-Maria Fendt (SM)

Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology (K. Vriens, S.-M.F.), KU Leuven.
Laboratory of Cellular Metabolism and Metabolic Regulation (K. Vriens, S.-M.F.), Center for Cancer Biology, VIB, Leuven.

Aileen Schroeter (A)

Institute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, UZH, Zurich, Switzerland (A. Seuwen, F.S., A. Schroeter).

Joanna Kalucka (J)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.
Aarhus Institute of advanced studies (AIAS) and Department of Biomedicine, Aarhus University (J.K.).

Anna Rita Cantelmo (AR)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.
Université de Lille, INSERM U1003, Physiologie Cellulaire, France (A.R.C.).

Thomas Wälchli (T)

Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich (UZH) and ETHZ and Division of Neurosurgery, USZ, Zurich (M.G., T.W.).
Group of Brain Vasculature and Neurovascular Unit, Department of Clinical Neurosciences, University Hospital Geneva (T.W.).
Department of Fundamental Neurobiology, Krembil Research Institute (T.W.), Toronto Western Hospital, University Health Network, University of Toronto.
Division of Neurosurgery, Department of Surgery (T.W.), Toronto Western Hospital, University Health Network, University of Toronto.

Annika Keller (A)

Neuroscience Center Zurich (J.S., A.K.), UZH/ETHZ, Zurich, Switzerland.
Department of Neurosurgery, Clinical Neurocentre, USZ, Zurich (J.S., A.K.).

Peter Carmeliet (P)

From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Laboratory of Angiogenesis and Vascular Metabolism (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), Center for Cancer Biology, VIB, Leuven.

Katrien De Bock (K)

Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).

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Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › AMP-Activated Protein Kinases › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Eucaryotes › Animaux › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Phénomènes physiologiques › Mouvement cellulaire › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Cellules › Cellules épithéliales › Cellules endothéliales › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Tissus › Épithélium › Endothélium › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Tissus › Épithélium › Endothélium › Endothélium vasculaire › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Métabolisme › Métabolisme énergétique › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Glucides › Sucres › Oses › Hexose › Glucose › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs de glucose par diffusion facilitée › Transporteur de glucose de type 1 › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Néovascularisation physiologique › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Organes des sens › Oeil › Rétine › Role of the GLUT1 Glucose Transporter in...
Recherchemedicale.com › Système cardiovasculaire › Vaisseaux sanguins › Vaisseaux rétiniens › Role of the GLUT1 Glucose Transporter in...