Hypoxia But Not Inflammation Augments Glucose Uptake in Human Macrophages Implications For Imaging Atherosclerosis With (18)Fluorine-Labeled 2-Deoxy-D-Glucose Positron Emission Tomography

OBJECTIVES: Patient studies suggest that positron emission tomography (PET) usingĀ  (18)fluorine-labeled 2-deoxy-D-glucose FdG can detect “active” atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. 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 FdG uptake signals observed clinically.

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.

PMID: 21798423

Posted in Nuclear Imaging and tagged , , , , , .

3 Comments

  1. Very technical paper! As the authors note, these in vitro and ex vivo experiments may not replicate the pathophysiological conditions in atheroma. However, they do add knowledge about the glucose uptake and metabolism associated to it which may help further understand the biologic basis of plaque and its vulnerability… as well as the meaning of FDG uptake by plaque.

  2. Accompanying editorial:

    Imaging atherosclerosis with f18-fluorodeoxyglucose positron emission tomography what are we actually seeing?
    Joseph C. Wu and Patricia K. Nguyen.
    J Am Coll Cardiol 2011;58 615-617.
    PMID: 21798424

  3. See also:

    Imaging of the aortic valve using fluorodeoxyglucose positron emission tomography increased valvular fluorodeoxyglucose uptake in aortic stenosis.
    Marincheva-Savcheva G, Subramanian S, Qadir S, Figueroa A, Truong Q, Vijayakumar J, Brady TJ, Hoffmann U, Tawakol A.
    J Am Coll Cardiol. 2011 Jun 21;57(25):2507-15.
    PMID: 21679852

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