In Vivo Fluorescence-mediated Tomography Imaging Demonstrates Atorvastatin-mediated Reduction of Lesion Macrophages in ApoE-/- Mice
In Vivo Fluorescence-mediated Tomography Imaging Demonstrates Atorvastatin-mediated Reduction of Lesion Macrophages in ApoE-/- Mice
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体内荧光介导的断层扫描成像显示阿托伐他汀介导的 ApoE-/- 小鼠病变巨噬细胞减少
DOI：
10.1097/aln.0b013e318291c18b
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发表时间：
2013
期刊：
影响因子：
8.8
通讯作者：
Theilmeier G
中科院分区：
文献类型：
--
作者：
Larmann J;Frenzel T;Schmitz M;Hahnenkamp A;Demmer P;Immenschuh S;Tietge UJ;Bremer C;Theilmeier G
巨噬细胞聚集到动脉粥样硬化斑块中驱动病变进展、不稳定和破裂。慢性他汀类药物治疗可减少巨噬细胞斑块含量。巨噬细胞募集的动态信息将有助于评估斑块易损性和指导治疗。巨噬细胞在体内归向易损斑块的成像技术很少。作者测试了无创荧光介导的断层扫描（FMT）是否可以评估短期大剂量阿托伐他汀的斑块稳定作用。方法采用近红外荧光染料标记绿色荧光蛋白转基因小鼠的巨噬细胞，在颈动脉导丝损伤7天后静脉注射载脂蛋白e缺乏小鼠（n= 9）。fmt扫描，2和7天后，量化巨噬细胞募集到颈动脉斑块。体外检测阿托伐他汀对巨噬细胞的粘附、增殖和活力（n= 5 ~ 6）。14只小鼠在西餐16周后给予4天阿托伐他汀或代药。FMT评估巨噬细胞在主动脉和无名动脉病变中的募集情况。报告平均值（±SD）%。结果双标记巨噬细胞被募集到颈动脉病变中。FMT分辨了投射在颈动脉上的荧光，检测到导丝损伤后信号增加了300%（±191）。阿托伐他汀减少巨噬细胞粘附活化内皮细胞36%（±19）。在一项临床相关的概念验证干预中，fmt成像检测到4天的阿托伐他汀治疗使巨噬细胞募集减少了57%（±8），表明斑块稳定。免疫组化证实巨噬细胞浸润减少。结论sfmt光学成像在体内追踪近红外荧光标记巨噬细胞向易损斑块募集方面具有很高的临床应用潜力。基于fmt的巨噬细胞募集定量显示，在载脂蛋白e缺乏小鼠中，阿托伐他汀治疗4天后，斑块快速稳定。
BackgroundMacrophage recruitment into atherosclerotic plaques drives lesion progression, destabilization, and rupture. Chronic statin treatment reduces macrophage plaque content. Information on dynamics of macrophage recruitment would help assessing plaque vulnerability and guiding therapy. Techniques to image macrophage homing to vulnerable plaques in vivo are scarcely available. The authors tested if noninvasive fluorescence-mediated tomography (FMT) can assess plaque-stabilizing effects of short-term high-dosage atorvastatin.MethodsMacrophages from green-fluorescent-protein-transgenic mice were labeled with a near-infrared fluorescent dye and were injected IV in apolipoprotein E-deficient mice (n= 9) on Western diet 7 days after guidewire-injury of the carotid artery. FMT-scans, 2 and 7 days thereafter, quantified macrophage recruitment into carotid artery plaques. Atorvastatin was tested for macrophage adhesion, proliferation, and viability (n= 5 to 6) in vitro. Fourteen mice received atorvastatin or vehicle for 4 days after 16 weeks on Western diet. FMT assessed macrophage recruitment into aortic and innominate artery lesions. Means (±SD)% are reported.ResultsDouble-labeled macrophages were recruited into carotid artery lesions. FMT resolved fluorescence projecting on the injured carotid artery and detected a signal increase to 300%(±191) after guidewire injury. Atorvastatin reduced macrophage adhesion to activated endothelial cells by 36%(±19). In a clinically relevant proof-of-concept intervention, FMT-imaging detected that 4 days atorvastatin treatment reduced macrophage recruitment by 57%(±8) indicating plaque stabilization. Immunohistochemistry confirmed reduced macrophage infiltration.ConclusionsFMT optical imaging proved its high potential for clinical applicability for tracking recruitment of near-infrared fluorescent-labeled macrophages to vulnerable plaques in vivo. FMT-based quantification of macrophage recruitment demonstrated rapid plaque stabilization by 4-day atorvastatin treatment in apolipoprotein E-deficient mice.
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影响因子：
2.8
作者：
Ntziachristos, Vasilis;Bremer, Christoph;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
15.9
作者：
Potteaux, Stephane;Gautier, Emmanuel L.;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
3.4
作者：
Christenson, JT
通讯作者：
Christenson, JT
影响因子：
37.8
作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
通讯作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
DOI：
10.1073/pnas.89.10.4471
发表时间：
1992-05-15
影响因子：
11.1
作者：
PIEDRAHITA, JA;ZHANG, SH;MAEDA, N
通讯作者：
MAEDA, N