Kircher Moritz F, Grimm Jan, Swirski Filip K, Libby Peter, Gerszten Robert E, Allport Jennifer R, Weissleder Ralph
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass, USA.
Circulation. 2008 Jan 22;117(3):388-95. doi: 10.1161/CIRCULATIONAHA.107.719765. Epub 2008 Jan 2.
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.
Using a micro-single-photon emission computed tomography small-animal imaging system and a Food and Drug Administration-approved radiotracer ([indium 111] oxyquinoline, (111)In-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.
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.
单核细胞在动脉粥样硬化形成过程中起关键作用，但其参与情况主要通过对动脉粥样硬化病变的体外分析来识别。我们试图建立一种非侵入性技术，以确定活体动物中单核细胞向动脉粥样硬化病变的迁移情况。
使用微型单光子发射计算机断层扫描小动物成像系统和美国食品药品监督管理局批准的放射性示踪剂（[铟111]羟基喹啉，111In-oxine），我们在此证明，在活体动物中可以以非侵入性、动态和三维方式可视化单核细胞向动脉粥样硬化病变的募集。我们在体内显示，在过继转移后的数天内，单核细胞会大量募集到斑块中。使用微型单光子发射计算机断层扫描成像作为筛选工具，我们能够研究对活体动物单核细胞募集的调节作用。我们发现，如在此体内成像所示，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂能迅速且显著减少单核细胞向现有动脉粥样硬化病变的募集。
这种在体内追踪单核细胞至动脉粥样硬化斑块的新方法应具有广泛的应用，并为动脉粥样硬化和其他炎症性疾病的发病机制带来新的见解。
