1. Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography.
- Author
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Folco EJ, Sheikine Y, Rocha VZ, Christen T, Shvartz E, Sukhova GK, Di Carli MF, and Libby P
- Subjects
- Aorta pathology, Atherosclerosis pathology, Cytokines metabolism, Endothelial Cells cytology, Fluorodeoxyglucose F18 pharmacology, Foam Cells metabolism, Glucose metabolism, Humans, Hydrolysis, Macrophages metabolism, Monocytes cytology, Myocytes, Smooth Muscle metabolism, Positron-Emission Tomography methods, Atherosclerosis diagnostic imaging, Atherosclerosis therapy, Glucose pharmacokinetics, Hypoxia, Inflammation, Macrophages drug effects
- Abstract
Objectives: This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the (18)fluorine-labeled 2-deoxy-D-glucose (FdG) uptake signals observed clinically., Background: Patient studies suggest that positron emission tomography (PET) using FdG can detect "active" atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown., Methods: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake., Results: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques-regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines., Conclusions: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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