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[SCIENTIFIC PUBLICATION] Company ; METAglut1™
We are excited to showcase new findings from Laurent Yvan-Charvet’s research team, who published in Circulation Research, titled “Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE(-/-) Mice“
This study investigates the critical role of Glut1 in hematopoietic stem cells and its impact on myelopoiesis and glucose metabolism within atheromatous plaques.
SCIENTIFIC PUBLICATION
Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE(-/-) Mice
Affiliations
1From the Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France (V.S., M.V., S.I., S.G.-P., R.G., L.Y.-C.); Division of Molecular Medicine, Department of Medicine (M.W.) and Department of Neurology (D.C.D.V.), Columbia University, New York, NY; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Hôpital de la Pitié, Paris, France (E.L.G.); Pierre & Marie Curie University, Université Paris 06, Paris, France (E.L.G.); Institute of Cardiometabolism and Nutrition (ICAN), Boulevard de l’Hôpital, Paris, France (E.L.G.); and Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL (E.B.T.).
2From the Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France (V.S., M.V., S.I., S.G.-P., R.G., L.Y.-C.); Division of Molecular Medicine, Department of Medicine (M.W.) and Department of Neurology (D.C.D.V.), Columbia University, New York, NY; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Hôpital de la Pitié, Paris, France (E.L.G.); Pierre & Marie Curie University, Université Paris 06, Paris, France (E.L.G.); Institute of Cardiometabolism and Nutrition (ICAN), Boulevard de l’Hôpital, Paris, France (E.L.G.); and Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL (E.B.T.). laurent.yvancharvet@unice.fr.
PMID: 26926469
PMCID: PMC4824305
Abstract
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.
Keywords: atherosclerosis; bone marrow; cholesterol; glucose transporter type 1; glycolysis; myeloid cells.
© 2016 American Heart Association, Inc.
