Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography

作者：Folco E J; Sheikine Y; Rocha V Z; Christen T; Shvartz E; Sukhova G K; Di Carli M F; Libby P^*

来源：Journal of the American College of Cardiology, 2011, 58(6): 603-614.

DOI：10.1016/j.jacc.2011.03.044

• 2-deoxy-D-glucose
• atherosclerosis
• fluorodeoxyglucose
• glucose transporter
• hexokinase
• hypoxia
• inflammation
• positron emission tomography
• statin

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 18fluorine-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 plaquesregions 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.

• 单位
  harvard medical school