Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging.
Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging.
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DOI：
10.1016/j.jcmg.2011.04.020
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发表时间：
2011-10
影响因子：
14
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Vucic, Esad;Dickson, Stephen D.;Calcagno, Claudia;Rudd, James H. F.;Moshier, Erin;Hayashi, Katsumi;Mounessa, Jessica S.;Roytman, Michelle;Moon, Matthew J.;Lin, James;Tsimikas, Sotirios;Fisher, Edward A.;Nicolay, Klaas;Fuster, Valentin;Fayad, Zahi A.
关键词：
我们试图用多模式非侵入性成像技术来确定吡格列酮的抗动脉粥样硬化特性。炎症是易损或高危动脉粥样硬化的重要组成部分。吡格列酮是一种过氧化物酶体增殖物激活受体-γ(PPAR-γ)激动剂，具有强大的抗炎作用。我们旨在利用18F-脱氧葡萄糖(18F-FDG)-PET/CT和动态增强MRI(DCE-MRI)无创定量评价吡格列酮对动脉粥样硬化的抗炎作用。用高脂饲料加两种球囊内皮剥脱法在15只新西兰大白兔的主动脉内建立动脉粥样硬化斑块模型。9只兔继续饲喂相同的饲料，6只在饮食的基础上加用吡格列酮(10 mg/kg)。12只动物接受了18F-FDG-PET/CT，15只动物在治疗开始后1个月和3个月接受了DCE-MRI检查。同时，监测血清代谢参数。成像完成后进行主动脉组织学分析及相关分析。18F-FDG-PET/CT检测到对照组的平均标准化摄取值(SUV)增加(p<；0.01)，表明炎症进展，而治疗组的SUV值稳定，表明没有进展。DCE-MRI检测到吡格列酮组的曲线下面积(AUC)显著减少(p<；0.01)。免疫组织学显示，与对照组动物相比，吡格列酮组大鼠主动脉巨噬细胞和氧化磷脂的免疫反应性显著降低(分别为p=0.04和p=0.01)，这突出了成像结果。血清代谢参数组间差异无统计学意义。SUV和巨噬细胞密度与AUC和新生血管数呈显著正相关(r2=0.86p<；0.0001和r2=0.66，p=0.004)。18F-FDG-PET/CT和DCE-MRI无创证实了吡格列酮对动脉粥样硬化的抗炎作用。这两种成像方式似乎都适合于监测动脉粥样硬化的炎症反应。
We sought to determine the anti-atherosclerotic properties of pioglitazone using multi-modality non-invasive imaging techniques. Inflammation is an essential component of vulnerable or high risk atheromas. Pioglitazone, a peroxisome proliferator–activated receptor-gamma (PPAR-γ)agonist possesses potent anti-inflammatory properties. We aimed to non-invasively to quantify the anti-inflammatory effects of pioglitazone on atheroma using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT and dynamic contrast enhanced MRI (DCE-MRI). Atherosclerotic plaques were induced in the aorta of fifteen New Zealand White (NZW) rabbits by a combination of hyperlipidemic diet and two balloon endothelial denudations. Nine rabbits continued the same diet whereas six received pioglitazone (10mg/kg orally) in addition to the diet. Twelve animals underwent 18F-FDG-PET/CT and fifteen animals underwent DCE-MRI at baseline, one and three months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed aortic histological analysis and correlation analysis was performed. 18F-FDG-PET/CT detected an increase in average standardized uptake value (SUV) in the control group (p<0.01), indicating progressive inflammation, while stable SUV values were observed in the treatment group, indicating no progression. DCE-MRI detected a significant decrease in area under the curve (AUC) for the pioglitazone group (p<0.01). Immunohistology of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p=0.04 and p=0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. A strong positive correlation between SUV and macrophage density and AUC and neovessels was detected ( r2=0.86, p<0.0001 and r2=0.66, p=0.004, respectively). 18F-FDG-PET/CT and DCE-MRI demonstrate non-invasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging modalities appear suited to monitor inflammation in atherosclerosis.
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影响因子：
24
作者：
Tawakol, Ahmed;Migrino, Raymond Q.;Fischman, Alan J.
通讯作者：
Fischman, Alan J.
影响因子：
15.9
作者：
Li, AC;Brown, KK;Glass, CK
通讯作者：
Glass, CK
影响因子：
168.9
作者：
Dormandy, JA;Charbonnel, B;Taton, J
通讯作者：
Taton, J
DOI：
10.1161/atvbaha.108.165563
发表时间：
2009-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Rudd JH;Hyafil F;Fayad ZA
通讯作者：
Fayad ZA
吡格列酮在鼠颈动脉粥样硬化中抑制体内炎症：通过双靶荧光分子成像进行新的检测。
DOI：
10.1161/atvbaha.110.206342
发表时间：
2010-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Chang K;Francis SA;Aikawa E;Figueiredo JL;Kohler RH;McCarthy JR;Weissleder R;Plutzky J;Jaffer FA
通讯作者：
Jaffer FA