Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis.
Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis.
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DOI：
10.1007/s12350-020-02479-5
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
Tavakoli S
中科院分区：
文献类型：
--
作者：
Demirdelen S;Mannes PZ;Aral AM;Haddad J;Leers SA;Gomez D;Tavakoli S
巨噬细胞分化成不同表型的代谢分化是利用正电子发射断层扫描（PET）非侵入性表征动脉粥样硬化斑块的机制相关靶标。碳-11 （11C）标记的醋酸酯是临床上可用的一种示踪剂，可在动脉粥样硬化斑块中积累，但其在动脉粥样硬化中的生物学和临床相关性尚不清楚。测定了apoE - / -小鼠头臂动脉中14c -醋酸盐摄取的组织学相关性。通过对小鼠巨噬细胞和人颈动脉内膜切除术标本进行两天的促炎（干扰素-γ+脂多糖）和消炎（白细胞介素-4）刺激，确定极化刺激对14c -醋酸盐摄取的影响。14c -乙酸在动脉粥样硬化区积聚。cd68阳性的单核/巨噬细胞与平滑肌肌动蛋白阳性的平滑肌细胞是14c -醋酸盐摄取高与低区域的优势细胞。促炎巨噬细胞的14c -乙酸摄取量逐渐下降至基线的25.9±4.5% （P<0.001）。消炎巨噬细胞的14c -乙酸摄取延迟增加，达到基线的164.1±21.4% （P<0.01）。与未刺激斑块相比，干扰素-γ+脂多糖刺激动脉内膜切除术标本使14c -醋酸盐摄取减少至66.5±14.5%，而白介素-4使14c -醋酸盐摄取增加至151.5±25.8% （P<0.05）。巨噬细胞对醋酸盐的摄取在促炎和消炎刺激下发生分化，这可能被用于动脉粥样硬化的免疫代谢表征。
Metabolic divergence of macrophages polarized into different phenotypes represents a mechanistically relevant target for non-invasive characterization of atherosclerotic plaques using positron emission tomography (PET). Carbon-11 (11C)-labeled acetate is a clinically available tracer which accumulates in atherosclerotic plaques, but its biological and clinical correlates in atherosclerosis are undefined. Histological correlates of 14C-acetate uptake were determined in brachiocephalic arteries of western diet fed apoE−/− mice. The effect of polarizing stimuli on 14C-acetate uptake was determined by pro-inflammatory (interferon-γ+lipopolysaccharide) vs. inflammation-resolving (interleukin-4) stimulation of murine macrophages and human carotid endarterectomy specimens over two days. 14C-acetate accumulated in atherosclerotic regions of arteries. CD68-positive monocytes/macrophages vs. smooth muscle actin-positive smooth muscle cells were the dominant cells in regions with high vs. low 14C-acetate uptake. 14C-acetate uptake progressively decreased in proinflammatory macrophages to 25.9±4.5% of baseline (P<0.001). A delayed increase in 14C-acetate uptake was induced in inflammation-resolving macrophages, reaching to 164.1±21.4% (P<0.01) of baseline. Consistently, stimulation of endarterectomy specimens with interferon-γ+lipopolysaccharide decreased 14C-acetate uptake to 66.5±14.5%, while interleukin-4 increased 14C-acetate uptake to 151.5±25.8% compared to non-stimulated plaques (P<0.05). Acetate uptake by macrophages diverges upon pro-inflammatory and inflammation-resolving stimulations, which may be exploited for immuno-metabolic characterization of atherosclerosis.
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影响因子：
30.5
作者：
Koelwyn GJ;Corr EM;Erbay E;Moore KJ
通讯作者：
Moore KJ
影响因子：
5.8
作者：
Puchalska P;Huang X;Martin SE;Han X;Patti GJ;Crawford PA
通讯作者：
Crawford PA
影响因子：
20.1
作者：
DAY, AJ;WILKINSON, GK
通讯作者：
WILKINSON, GK
影响因子：
37.8
作者：
ARMBRECHT, JJ;BUXTON, DB;SCHELBERT, HR
通讯作者：
SCHELBERT, HR
DOI：
10.1007/s002590050480
发表时间：
1999-11-01
期刊：
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
影响因子：
--
作者：
Porenta, G;Cherry, S;Schelbert, HR
通讯作者：
Schelbert, HR