Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE−/− Mice
| Autor: | Vincent Sarrazy, Sophie Giorgetti-Peraldi, Laurent Yvan-Charvet, Darryl C. De Vivo, Stoyan Ivanov, Edward B. Thorp, Manon Viaud, Emmanuel L. Gautier, Marit Westerterp, Rodolphe Guinamard |
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| Přispěvatelé: | Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Columbia University [New York], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Northwestern University [Chicago, Ill. USA], Gautier, Emmanuel, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Translational Immunology Groningen (TRIGR) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Apolipoprotein E
MESH: Myelopoiesis MESH: Cytokine Receptor Common beta Subunit MESH: Spleen Aorta Thoracic/metabolism MESH: Metformin Cytokine Receptor Common beta Subunit Mice Glucose/metabolism MESH: Animals MESH: Bone Marrow Transplantation ComputingMilieux_MISCELLANEOUS Bone Marrow Transplantation Myelopoiesis Multipotent Stem Cells/metabolism Hypoxia-Inducible Factor 1 alpha Subunit/deficiency Glucose analog Metformin Plaque Atherosclerotic 3. Good health [SDV] Life Sciences [q-bio] Disease Progression MESH: Cell Division MESH: Disease Progression Hypoxia-Inducible Factor 1 Cardiology and Cardiovascular Medicine Cell Division Myelopoiesis/physiology Atherosclerotic/metabolism alpha Subunit/deficiency Knockout MESH: Aorta Thoracic Hypercholesterolemia Article 03 medical and health sciences Apolipoproteins E Plaque Atherosclerotic/metabolism MESH: Plaque Atherosclerotic RNA Messenger Progenitor cell MESH: Tyrphostins cholesterol Apolipoproteins E/deficiency Hematopoietic Stem Cells Messenger/biosynthesis Receptors Interleukin-3 Mice Inbred C57BL 030104 developmental biology Glucose Immunology atherosclerosis MESH: Multipotent Stem Cells MESH: Glucose Transporter Type 1 0301 basic medicine Physiology [SDV]Life Sciences [q-bio] Glucose uptake Cytokine Receptor Common beta Subunit/physiology Glucose Transporter Type 1/deficiency Aorta Thoracic Spleen/metabolism Inbred C57BL MESH: Mice Knockout MESH: Hematopoietic Stem Cells Metformin/pharmacology Receptors Hematopoietic Stem Cells/metabolism Interleukin-3/antagonists & inhibitors Aorta Plaque Mice Knockout Glucose Transporter Type 1 MESH: Energy Metabolism MESH: Hypercholesterolemia Tyrphostins MESH: Apolipoproteins E MESH: Gene Expression Regulation MESH: Glucose Haematopoiesis medicine.anatomical_structure myeloid cells MESH: Glycolysis Stem cell Glycolysis Hypercholesterolemia/genetics bone marrow Biology Thoracic/metabolism Receptors Interleukin-3/antagonists & inhibitors MESH: Receptors Interleukin-3 MESH: Hypoxia-Inducible Factor 1 alpha Subunit MESH: Mice Inbred C57BL Tyrphostins/pharmacology medicine Animals MESH: Mice MESH: RNA Messenger Multipotent Stem Cells RNA Messenger/biosynthesis Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Gene Expression Regulation RNA Bone marrow Energy Metabolism Spleen |
| Zdroj: | Circulation Research Circulation Research, 2016, 118 (7), pp.1062-1077. ⟨10.1161/CIRCRESAHA.115.307599⟩ Circulation Research, American Heart Association, 2016, 118 (7), pp.1062-1077. ⟨10.1161/circresaha.115.307599⟩ Circulation research, 118(7), 1062-1077. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 0009-7330 1524-4571 |
| DOI: | 10.1161/CIRCRESAHA.115.307599⟩ |
| Popis: | Rationale: Inflamed atherosclerotic plaques can be visualized by noninvasive positron emission and computed tomographic imaging with 18 F-fluorodeoxyglucose, a glucose analog, but the underlying mechanisms are poorly understood. Objective: Here, we directly investigated the role of Glut1-mediated glucose uptake in apolipoprotein E–deficient ( ApoE −/− ) mouse model of atherosclerosis. Methods and Results: We first showed that the enhanced glycolytic flux in atheromatous plaques of ApoE −/− mice was associated with the enhanced metabolic activity of hematopoietic stem and multipotential progenitor cells and higher Glut1 expression in these cells. Mechanistically, the regulation of Glut1 in ApoE −/− hematopoietic stem and multipotential progenitor cells was not because of alterations in hypoxia-inducible factor 1α signaling or the oxygenation status of the bone marrow but was the consequence of the activation of the common β subunit of the granulocyte-macrophage colony-stimulating factor/interleukin-3 receptor driving glycolytic substrate utilization by mitochondria. By transplanting bone marrow from WT, Glut1 +/− , ApoE −/− , and ApoE −/− Glut1 +/− mice into hypercholesterolemic ApoE-deficient mice, we found that Glut1 deficiency reversed ApoE −/− hematopoietic stem and multipotential progenitor cell proliferation and expansion, which prevented the myelopoiesis and accelerated atherosclerosis of ApoE −/− mice transplanted with ApoE −/− bone marrow and resulted in reduced glucose uptake in the spleen and aortic arch of these mice. Conclusions: We identified that Glut1 connects the enhanced glucose uptake in atheromatous plaques of ApoE −/− mice with their myelopoiesis through regulation of hematopoietic stem and multipotential progenitor cell maintenance and myelomonocytic fate and suggests Glut1 as potential drug target for atherosclerosis. |
| Databáze: | OpenAIRE |
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