Noninvasive Imaging of Angiotensin Receptors After Myocardial Infarction
Noninvasive Imaging of Angiotensin Receptors After Myocardial Infarction
复制标题
DOI：
10.1016/j.jcmg.2007.11.007
复制
发表时间：
2008-05-01
影响因子：
14
通讯作者：
Narula, Jagat
中科院分区：
文献类型：
--
作者：
Verjans, Johan W. H.;Lovhaug, Dagfinn;Narula, Jagat
目的：本研究的目的是评估血管紧张素II （AT）受体在心肌梗死后（MI）心力衰竭（HF）小鼠模型中的无创成像的可行性。背景循环AT水平不能反映心肌肾素-血管紧张素轴的上调状态，而肾素-血管紧张素轴在心肌梗死后心室重构和心衰演变中起着核心作用。适当标记的AT或AT受体阻滞剂应该能够通过分子成像技术特异性靶向AT受体。方法使用荧光血管紧张素肽类似物（APA）和放射性标记氯沙坦，在永久性冠状动脉结扎后的不同时间点对29只小鼠或对照组进行AT受体成像。APA用于19只动物的活体荧光显微镜下跳动的小鼠心脏。采用Tc-99m氯沙坦对10只小鼠进行体内放射性核素显像和AT受体表达定量评估。成像后，采集心脏，用共聚焦和双光子显微镜进行病理表征。结果对照动物和梗死区在第0天和第1天没有或很少观察到APA摄取。心肌梗死后1 ~ 12周，梗死区出现明显摄取；心肌梗死后3周时摄取最大，12周时明显减少。超声检查显示左心室重构，病理特征显示APA示踪剂与产生胶原的肌成纤维细胞定位。梗死区Tc-99m氯沙坦摄取（注射剂量/g 0.524 +/- 0.212%）比对照动物（0.215 +/- 0.129%,p < 0.05）增加2.4倍。结论本研究证实了AT受体在重构心肌中的体内分子成像的可行性。针对at受体表达的无创成像研究可以在识别可能发生心力衰竭的受试者中发挥作用。此外，这种策略可以优化心肌梗死后患者的抗血管紧张素治疗。（J Am Coll Cardiol Img 2008; 1: 354-62） (C) 2008由美国心脏病学会基金会
OBJECTIVES The purpose of this study was to evaluate the feasibility of noninvasive imaging of angiotensin II (AT) receptor upregulation in a mouse model of post-myocardial infarction (MI) heart failure (HF).BACKGROUND Circulating AT levels do not reflect the status of upregulation of renin-angiotensin axis in the myocardium, which plays a central role in ventricular remodeling and evolution of HF after MI. Appropriately labeled AT or AT receptor blocking agents should be able to specifically target AT receptors by molecular imaging techniques.METHODS AT receptor imaging was performed in 29 mice at various time points after permanent coronary artery ligation or in controls using a fluoresceinated angiotensin peptide analog (APA) and radiolabeled losartan. The APA was used in 19 animals for intravital fluorescence microscopy on a beating mouse heart. Tc-99m losartan was used for in vivo radionuclide imaging and quantitative assessment of AT receptor expression in 10 mice. After imaging, hearts were harvested for pathological characterization using confocal and 2-photon microscopy.RESULTS No or little APA uptake was observed in control animals or within infarct regions on days 0 and 1. Distinct uptake occurred in the infarct area at 1 to 12 weeks after MI; the uptake was at maximum at 3 weeks and reduced markedly at 12 weeks after MI. Ultrasonographic examination demonstrated left ventricular remodeling, and pathologic characterization revealed localization of the APA tracer with collagen-producing myofibroblasts. Tc-99m losartan uptake in the infarct region (0.524 +/- 0.212% injected dose/g) increased 2.4-fold as compared to uptake in the control animals (0.215 +/- 0.129%; p < 0.05).CONCLUSIONS The present study demonstrates the feasibility of in vivo molecular imaging of AT receptors in the remodeling myocardium. Noninvasive imaging studies aimed at AT receptor expression could play a role in identification of subjects likely to develop heart failure. In addition, such a strategy could allow for optimization of anti-angiotensin therapy in patients after MI. (J Am Coll Cardiol Img 2008; 1: 354-62) (C) 2008 by the American College of Cardiology Foundation