Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions
Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions
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DOI：
10.1161/circulationaha.107.719765
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发表时间：
2008-01-22
期刊：
影响因子：
37.8
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Kircher, Moritz F.;Grimm, Jan;Weissleder, Ralph
背景-单核细胞在动脉粥样硬化形成中起关键作用，但它们的参与主要是通过动脉粥样硬化病变的体外分析来识别的。我们试图建立一种非侵入性的技术来确定单核细胞运输到动脉粥样硬化病变的活动物。方法和结果-使用微型单光子发射计算机断层扫描小动物成像系统和食品和药物管理局批准的放射性示踪剂（[铟111]羟基喹啉，In-111-oxine），我们在这里证明，单核细胞募集到动脉粥样硬化病变可以在一个非侵入性，动态，和三维的时尚。我们在体内表明，单核细胞在过继转移的几天内被贪婪地招募到斑块。使用微单光子发射计算机断层扫描成像作为筛选工具，我们能够调查调节作用的单核细胞募集活的动物。我们发现，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂迅速，大大减少单核细胞招聘现有的动脉粥样硬化病变，成像在vivo. Conclusions，这种新的方法来跟踪单核细胞动脉粥样硬化斑块在体内应该有广泛的应用，并创造新的见解动脉粥样硬化和其他炎症性疾病的发病机制。
Background-Monocytes play a key role in atherogenesis, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. We sought to establish a noninvasive technique to determine monocyte trafficking to atherosclerotic lesions in live animals.Methods and Results-Using a micro-single-photon emission computed tomography small-animal imaging system and a Food and Drug Administration-approved radiotracer ([ indium 111] oxyquinoline, In-111-oxine), we demonstrate here that monocyte recruitment to atherosclerotic lesions can be visualized in a noninvasive, dynamic, and 3-dimensional fashion in live animals. We show in vivo that monocytes are recruited avidly to plaques within days of adoptive transfer. Using micro-single-photon emission computed tomography imaging as a screening tool, we were able to investigate modulatory effects on monocyte recruitment in live animals. We found that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors rapidly and substantially reduce monocyte recruitment to existing atherosclerotic lesions, as imaged here in vivo.Conclusions-This novel approach to track monocytes to atherosclerotic plaques in vivo should have broad applications and create new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.