Noninvasive monitoring the biology of atherosclerotic plaque development with radiolabeled annexin V and matrix metalloproteinase inhibitor in spontaneous atherosclerotic mice.
Noninvasive monitoring the biology of atherosclerotic plaque development with radiolabeled annexin V and matrix metalloproteinase inhibitor in spontaneous atherosclerotic mice.
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使用放射性标记的膜联蛋白 V 和基质金属蛋白酶抑制剂在自发性动脉粥样硬化小鼠中无创监测动脉粥样硬化斑块发展的生物学。
DOI：
10.1007/s12350-010-9276-5
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Johnson,LynneL
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文献类型：
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作者：
Tekabe,Yared;Li,Qing;Luma,Joane;Weisenberger,Drew;Sedlar,Marija;Harja,Evis;Narula,Jagat;Johnson,LynneL
目的比较99 mTc标记的广谱基质金属蛋白酶抑制剂（RP 805）（MPI）和99 mTc-膜联蛋白V在载脂蛋白E-null（apoE-/-）小鼠中识别更晚期动脉粥样硬化疾病的能力。背景MMP表达和凋亡细胞死亡均发生在早期和晚期动脉粥样硬化斑块中。和12个apoE−/−在40周时以间隔48 h的交替顺序注射两种示踪剂，进行平面成像并处死。放射性示踪剂摄取从扫描中定量为全身百分比，从组织中定量为每克注射剂量百分比（%ID/g）。巨噬细胞，基质金属蛋白酶，和半胱天冬酶的主动脉和颈动脉的定量免疫组织病理学performed.ResultsAt 6周，小鼠在胸部或颈部没有示踪剂摄取，并有最小的病变。在20周时，膜联蛋白V的摄取（以%ID表示）高于MPI（1.10 ±.48%vs.77 ±.31%，P = .09），在20周和40周之间，主动脉病变面积从37.4 ± 12.0%增加到46.2 ± 7.4%，并且在40周时MPI显著大于膜联蛋白V摄取（1.11 ±.66%vs.70 ±.16%，P = .05）。在组织学上，% MMP-2和-9的增加大于%半胱天冬酶阳性细胞。在20周和40周，MPI的颈动脉摄取均大于膜联蛋白V（1.25 ±.48%vs.78 ±.25%，P = .02和3.70 ± 1.45%vs2.25 ±.66%，P = .005）。40周时颈动脉病变面积为74 ± 9%，MMP阳性细胞百分比高于caspase阳性细胞百分比。%ID/g膜联蛋白V与%巨噬细胞和caspase-3阳性细胞显着相关，%ID/g MPI与%巨噬细胞和MMP-2和-9阳性cells.ConclusionsIn apoE−/−mice，MMP表达大于凋亡，随着疾病的进展和MPI可能是一个更好的成像剂更先进的疾病。
ObjectivesTo compare the ability of99mTc-labeled broad-based matrix metalloproteinase inhibitor (RP805) (MPI) and99mTc-annexin V to identify more advanced atherosclerotic disease in apolipoprotein E-null (apoE−/−) mice.BackgroundBoth MMP expression and apoptotic cell death occur in both early and in advanced atherosclerotic plaques.MethodsEight 6-9-week-old apoE−/−mice, 10 apoE−/−mice at 20 weeks, and 12 apoE−/−at 40 weeks were injected with both tracers in alternating sequence separated by 48 h, underwent planar imaging and were killed. Radiotracer uptake was quantified from the scans as percent whole body and from tissue as percent injected dose per gram (%ID/g). Quantitative immunohistopathology of the aorta and carotids for macrophages, MMPs, and caspase was performed.ResultsAt 6 weeks, mice showed no tracer uptake in the chest or neck and had minimal lesion. At 20 weeks, uptake of annexin V as %ID was borderline higher than MPI (1.10 ± .48% vs .77 ± .31%,P= .09), between 20 and 40 weeks aortic lesion area increased from 37.4 ± 12.0% to 46.2 ± 7.4% and at 40 weeks MPI was significantly greater than annexin V uptake (1.11 ± .66% vs .70 ± .16%,P= .05). On histology there were greater increases in % MMP-2 and -9 than % caspase positive cells. Carotid uptake of MPI was greater than annexin V at both 20 and 40 weeks (1.25 ± .48% vs .78 ± .25%,P= .02 and 3.70 ± 1.45% vs 2.25 ± .66%,P= .005). The carotid lesion area at 40 weeks was 74 ± 9% with greater % cells positive for MMP’s than caspase. %ID/g annexin V correlated significantly with % macrophages and with caspase-3 positive cells and %ID/g MPI correlated significantly with % macrophages and with MMP-2 and -9 positive cells.ConclusionsIn apoE−/−mice, MMP expression is greater than apoptosis as the disease progresses and MPI may be a better imaging agent for more advanced disease.