Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Am Coll Cardiol. 2011 Aug 2;58(6):603-14. doi: 10.1016/j.jacc.2011.03.044.
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.
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.
We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake.
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.
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.
本研究通过与动脉粥样硬化过程相关的刺激物来研究参与动脉粥样硬化形成的细胞中葡萄糖摄取的调节，以深入了解临床观察到的（18）氟标记 2-脱氧-D-葡萄糖（FdG）摄取信号的起源的机制。
患者研究表明，使用 FdG 的正电子发射断层扫描（PET）可以检测到“活跃”的动脉粥样硬化斑块，但产生 FdG 信号的机制尚不清楚。
我们将细胞暴露于被认为在动脉粥样斑块中起作用的条件下，并确定葡萄糖摄取的速率。
低氧而非促炎细胞因子强烈刺激人巨噬细胞和泡沫细胞的葡萄糖摄取。他汀类药物在体外减弱了这一过程，表明这些药物对人巨噬细胞有直接影响。对人斑块的免疫组织化学研究显示，调节葡萄糖利用的蛋白质大量表达，主要在斑块中富含巨噬细胞的区域——这些区域先前被证明存在缺氧。暴露于促炎细胞因子时，平滑肌细胞和内皮细胞明显增加葡萄糖摄取率。
动脉粥样硬化中葡萄糖摄取和（可能）FdG 摄取信号可能反映了受低氧刺激的巨噬细胞，而不仅仅是炎症负担。细胞因子激活的平滑肌细胞也可能对 FdG 信号有贡献。
